The Grim Adventures of Billy & Mandy/WMG

Grim and all other supernatural beings were not real... At first.
Mandy is so world-shatteringly powerful, that she can blur the line between metaphysical and physical. Luckily, Billy is so world-shatteringly stupid that the various Eldritch Abominations come out as the silly, quirky characters they are. If either Billy or Mandy were to die, the universe would dissolve into pure Darkness or Stupidity, as appropriate for the surviving one.

Grim is forced to repeatedly revive the characters whenever they die.
Over the course of the show, many of the characters have been seen dying, only to return in the next episode(usually regarded as Negative Continuity). In one episode, Grim is seen as being capable of allowing someone to live longer by putting more sand into his or her lifetimer. Since Grim is forced to be Billy and Mandy's best friend forever, that could mean that in order to live up to his end of the bargain, Billy and Mandy literally have to live FOREVER, meaning that he must bring them back to life whenever they get themselves killed. When any other characters die, Mandy probably orders Grim to revive them as well so she doesn't lose any of her future minions. And when Grim dies...well, he's the Grim Reaper, so he can probably revive himself.

Being Mandy is Adolf Hitler's Ironic Hell.
He's a little girl, but the universe underestimated him.

Mandy is the ultimate evil of the multiverse, although she's not entirely aware of it.
This would of course, make her the Evil Counterpart of.
 * And the Anti-Monitor.
 * And once she realises this,there will be an epic battle between her and the rest of the Cartoon Network multiverse
 * This is a given in a fanwork by the creator of The Powerpuff Girls Doujin.
 * Well, it seems like she at least knows it to the extent that she can control the whole of Endsville, and possibly beyond (watch the episode where Grim and Billy call the Nanny on her).
 * No, you've got it all wrong. She's the Evil Counterpart of Ruby Gloom. Seriously, they're complete opposites in every conceivable way.
 * Eons ago, an Ultimate Evil once dominated the underworld, having near-absolute control. It had total control over death, so it was immortal. It was also immune to almost any form of karma. One of Grim's ancestors managed to defeat this evil, by trapping it in a mortal body. However this being swore that, if it ever saw one of his/her ilk, it would have his revenge. Mandy was the ultimate result: This Ultimate Evil had passed its essence down generation after generation, until it reached her. Mandy was naturally moody and somewhat sociopathic to begin with, so the moment she won the bet, the Ultimate Evil began to awake. Luckily, Mandy only contains the soul of this being and not the memories, so she can't fully access her dark powers. Her parents weren't terrified of her until her dark powers awoke, and though Grim reaped her ancestors, he never was close enough to them to trigger this.
 * Alternate theory: She could very well be Aku, who after Samurai Jack returned from the future and struck the final blow, what remained of Aku transferred itself into a mortal body, which passed on for generations since.

Mandy's real parents are Sauron and Cruella de Ville.
She was adopted at birth.
 * Sadly, Jossed in the episode with Grim's Trial and Fred Fredberger. She's only the Reincarnation of the offspring of Sauron and Cruella De Ville.
 * She is also a baseline for measuring evil.
 * I must point out that the hypothetical offspring of Sauron and Cruella de Ville only registers at around  and when I built a detector of evil it registered Mandy at 999.99 Yottanazis before it exploded. Which means she is something far worse than the Reincarnation of the offspring of Sauron and Cruella De Ville.
 * 999.99?, Mandy isn't a Complete Monster.

Mandy is the reincarnation of Chernabog
Remember "Dream a Little Dream?" That wasn't a nightmare. That was a past-life memory.

Mandy is Eris' daughter
Her adoptive parents didn't really know how to pronounce and/or spell Dysnomia, and then, just named her Amanda... Or just Mandy, anyways. That's why Eris is so much time around them, even for being a deity. And Dysnomia was, indeed, smarter than her mom in the original mythology.
 * So that's where she got her blonde hair.

Mandy is Johan Liebert's daughter
Well, it explains how she got so many Yottanazis in above troper's detector.

Mandy is Eris' and Johan Liebert's daughter
What, it'd be awesome. Also, it would explain everything.

Grim, his granny, and Nergal are secretly high-class chefs
Why else would their food be so goddamn delicious?

The Series takes place in the early 80s, and Billy grows up to be Fry on Futurama.
Simultaneously, Mandy went into business and marketing after overthrowing Santa Claus and taking over the toy shop. The jolly old man and his wife were replaced by evil robots and Mandy renamed herself "Mom" in order to execute her mass rebranding scheme. Fearful of her eternal fate, she cryogenically froze herself as an old lady and soon Mom's Robot Oil became feared the world over.
 * Alas: a flashback in one episode shows Billy's dad in high school with a pink t-shirt that says "RELAX" on it.
 * That's just Billy's Dad's faulty memory. He is an idiot, after all.
 * They have giant plasma screen TVs and disc-based video games. Pretty advanced for the 80's.

The Dune-esque future where Mandy has enslaved the world might have been averted...
...If only Grim hadn't revealed it to Mandy, thus diverting the flow of time into an unavoidable destination.

Sassy Cat actually stands for the Sassy Kat Showclub
That's why Billy and Irwin love it so much.

Jack's Deal with Death was made to counteract his Deal with the Devil.

 * In folklore, Jack got the Devil to agree not to take his soul when he died after scamming him twice.
 * One of the solutions on the Deal with the Devil page is to wish for immortality.

Mandy is Vicky
If we assume that the show takes place in the 90's and Fairly Odd Parents takes place in the 2000's, it would make Mandy the right age to be Vicky. Notice how in both shows her parents are scared silly of her, and the drawing styles are similar. She simply dyed her hair and took on a new name as to make people less suspious of her after her previous actions. As for the nose...It grew back. As for the personality, well...its obvious they're both Complete monsters. In one episode Mandy has a crush on a guy and starts being...normal. Vicky is also at her most normal when she is with teenage boys. Her parents had Tootie in the hope that a sister would balance her out. It didn't.
 * However, this would mean that with age came lack of competence. Vicky often failed with consequences, but Mandy almost NEVER failed and is a Karma Houdini.
 * Puberty will make fools of us all...And she does succeed in making her victems lose the will to live.
 * If true, this could be a true sign of the Competence Zone and when it starts to take place.
 * During their wacky hijinks,they resurrected the god of karma.Causing it to hit Mandy like a ton of bricks.And then it created fairies to make the Earth less of a Crapsack World.To some extent.
 * The problem is technology is more advanced in Billy and Mandy. They have tiny cube shaped TVs and cartridge-based video games in Fairly Oddparents. As with the "Billy grows up to be Fry" WMG above, Billy and Mandy has giant plasma screen TVs and disc-based video games.
 * This might sound random, but Vicky's parents' names are Nikki and Vic. Mandy's parents are named Phil and Claire. Is Vicky-Teen-Mandy in some kind of foster care?

Mandy can tap into the dark forces of the Underworld.
Due to being with Grim for so long,Mandy has absorbed the energy of the underworld.Due to her incredible willpower,she has been able to tap into that energy.She used this to overwhelm Grim's magic and control the inhabitants of Endsville.This has also caused her personality to alter from a Jerkass to the Anti Christ
 * I don't think Grim had anything to do with it. She had those forces all along..

Billy is Obfuscating Stupidity.
The truth is Billy is the most intelligent person in the universe. He simply has to contain it as it would cause reality itself to distort around him
 * Alternatively, he realises that Mandy is the Anti Christ-so he pretends to be utterly stupid in order to ensure he can take down Mandy without her knowing.

In "My Fair Mandy", reality was broken by Mandy forcing a smile.
Mandy has been seen to smile other times in the series, without the same consequence. Notably her true, non-evil smile in the episode "Crushed", where she falls in love. Reality fell apart not because she smiled, but because she forced a smile. (Also, in the Christmas episode, Grim and Count von Goulash held her mouth open in a smile, so perhaps that didn't count because she wasn't forcing it?)
 * Good point. I never thought of that.

Nergal is Slender Man.
My first thought when I first heard about Slenderman. Nergal is a lanky humanoid creature in a suit, with retractable tentacles who kidnaps children. Can't be a coincidence.

Grim will eventually kill off Billy and Mandy
Think about it - sure, the deal was that Grim would be Billy and Mandy's "friend" forever, but he never promised them immortality, right? At least as far as I know anyway. I think he's just faking being stuck with them, and there's probably some massive backstory concerning Mandy being such a Karma Houdini. One day, Grim will kill Billy, and Mandy will try to avoid him, but he'll catch up eventually, and then turn the tables on her. He might even throw in an Ironic Hell, putting her in a similar situation to that episode with the mask (forget what it was though).
 * I think it's the inverse-Grim is forced to keep them alive, to ensure they are "friends forever." Of course, that may give him the revenge he wants. All he needs is patience.

Mandy is the Anti-Christ!
It is really obvious only something as evil and wickedly wicked could be the father of Mandy. The Devil had naughty-love with Mandy's Mom, possibly disguised as Mandy's supposed dad, and impregnated her with Mandy. She already became president of Earth during the Underfist special, it's only a matter of time she gets to (or above) her father's level!
 * Just to continue on this, Mandy will either usurp her father's position, an act the Devil will be proud of. After taking over the universe and turning it into Mordor, she will plot to take over Cartoon Network. She will be stopped by Billy, who is The Chosen Zero. And it will be purely by accident.
 * So, Billy is the Second Coming?
 * Maybe...At least, the Cartoon Network mulitverse' version of it.
 * This means she's the daughter of Him, who is the official Satan of Cartoon Network. Yeah, I know about Lucius, but Lucifer and Satan aren't necessasarily the same people.

Mandy is Rose Lalonde.
From Homestuck. Both are incredibly smart, blonde, and have a love of all things evil. Their associated colours are both pink and they have very similar haircuts. The events of "The Prank Call of Cthulu" inspire her to research Eldritch Abominations. Her mom hid behind a veil of Obfuscating Stupidity and changed Mandy's name to Rose when they left Endsville. Living alone, she learned how to like people (and thus became friends with John, Dave and Jade).

"Keeper of the Reaper" was one big analogy for/TakeThat at the American Supreme Court.

 * Okay, bear with me here... Fred Fredburger represents the U.S. Constitution as it applies to American law: he's often vague, typically unhelpful, and just about nigh-incomprehensible to everyone. And yet, the trial ends up hinging on him. Here's where the fun part comes in: all throughout the episode, the judge is driven bonkers by Fred's antics, but when the time comes to declare a verdict, he finally realizes that he can "interpret" Fred's nonsense to mean whatever the hell he wants it to mean, and no one can challenge him. The Founding Fathers, after all, intended for the Constitution to be as flexible as humanly possible, so that all the competing political parties could use it to their advantage. Luckily for all parties involved in this case, the stakes were small - the judge just wanted the damn trial to end as quickly as possible (and never see Billy & Mandy again).
 * New favourite WMG right here.

Irwin is a minor Humanoid Abomination.
Let's think about it: his grandfather is Dracula. That's odd enough, but at least Dracula is capable of breeding. His mother, on the other hand, is a mummy. By all rights, an undead Egyptian should not be able to bear a child. My theory is that, in order to have a child, they used a Tome of Eldritch Lore to defy the laws of nature, and as a result Irwin is fundamentally wrong. However, since it was just a child, it isn't as dangerous as, say, Cthulhu. The reason he continues to harass Mandy is due to the fact she harnesses Grim, and also seems to be wrong at some level. Since the universe dislikes Cosmic Horror incursions, Irwin is a Butt Monkey ala Kenny. He doesn't die a lot because