Philosopher's Stone

According to legend, the Philosopher's Stone is a red rock (though not always red or a rock), created by either magic or alchemy which allows you to do any number of things, including transmuting any metal into gold, and allowing you to live forever through an elixir of life.

And in settings where Alchemy Is Magic, it usually turns Alchemy Up to Eleven, giving the person using it almost godlike powers. Unfortunately, like most MacGuffins it comes with some sort of catch, either involving sacrificing humans, or something equally repugnant.

Note that this cost is largely only in fiction: in most alchemical modes of thought, the Philosopher's Stone was a metaphor for, or result of, achieving a sort of Gnostic enlightenment, where your knowledge and self control reach the height of human potential (or even beyond, in which case you transcend the worries of the mortal world to join with God). The reason the Stone isn't common is simply that most people simply don't have the capacity or experience to reach this state, and even those who have likely wouldn't have the desire to use the thing anyway, what with being what essentially amounts to a mental Physical God and all. An often overlooked fact is that to get it, you must not want to use its power. Or, more specifically, in order to attain it, you must have reached a degree of spiritual enlightenment that renders you content with your lot in life and, as such, do not feel any need to make use of the stone's more profane (ie: non-spiritual, like the turning lead into gold bit) properties.

It's less that you are unwilling to use it, and more that you don't feel the need to use it. It should also be noted that some sources claim that the immortality was a result of the process required to forge the stone, rather than being a property of the stone itself -- by the time you're able to make the philosopher's stone, you no longer need it.

Anime & Manga

 * Slayers featured a version of the Philosopher's Stone, though one with not much in common with the original myth. This Philosopher's Stone had the property of amplifying magic a hundredfold. It ended up being swallowed by the Dark Lord Shabranigdu and presumably destroyed. There is no know way to produce a new one, as the Stone was a unique legendary artifact. Lina claims it was a piece chipped off the staff that supports the world; it's true origin is revealed in the final light novel to be.
 * In Fullmetal Alchemist, the Philosopher's Stone has the power to violate the law of equivalent exchange in alchemy, but it comes at a terrible price: the stone is composed of human souls. It is even worse in the 2003 anime adaptation, where thousands of souls are required to create a single stone.
 * It turns out that the stone actually does not allow one to violate the law of equivalent exchange. As it happens, the stone actually acts like a massive battery for the alchemist, allowing them to perform energy-to-matter conversions which look to an outsider to be a total violation of equivalent exchange. Those human souls are converted into a "high-energy substance" which makes up the stone.
 * The Soft Stone in Karakuri Circus is used to created Aqua Vitae, "Water of Life", which is used in the creation of Shiroganes.
 * It was shown as an OOPArt artifact in Spriggan when Yu Ominae and Yoshino Somei team up to take down Koga-trained ninjas deployed to secure it during the former's field trip.
 * In their attempts to make a Philosopher's Stone, the alchemists of Busou Renkin made the kakugane, which, while not granting immortality, do give a Healing Factor. The Black Kakugane gets even closer,

Comic Books

 * Flash villain Doctor Alchemy has the Philosphers' Stone, and uses its powerful ablilty to transmute any element to commit crimes. Yup he uses something 'that can turn anything to pure gold to rob banks. On the bright side, he hasn't collapsed the DC Universe's gold market.
 * The Fantastic Four villain Diablo, a centuries-old alchemist once used the stone to increase his alchemical powers. His goal of world domination makes a bit more sense then just trying to get rich.

Literature

 * Appears, naturally enough, in Harry Potter And The Sorcerer's Philosopher's Stone, displaying its traditional powers of turning lead to gold and creating the elixir of life.
 * Used In The Alchemist. After all, it's the title character's Personal Legend.

Tabletop Games

 * In the Deadlands Weird West game, there is a modification to the Mad Scientist template that allows you to make an Alchemist character—these characters create the Philosopher's Stone as an everyday ingredient in even the simplest of their magical potions. However, its implied that there are few Alchemists compared to their more mundane steampunk counterparts, so there remains a degree of "enlightenment" to the template. Further, the game invokes the "cost" aspect of the trope, in that each dose of Philosopher's Stone requires the Alchemist to sacrifice a bit of blood, doing damage proportional to the amount you're trying to create. The game also subverts the spiritual aspect of the stone:
 * In Pathfinder, the Philosopher's Stone is a minor artifact. It takes the form of a small bit of black rock which can be broken open to find a small bit of quicksilver. This quicksilver can be used to turn large amounts of iron into silver or lead into gold, and can also be mixed with a cure potion to bring someone back to life with none of the usual level drain being resurrected causes. At 20th level, the alchemist base class can choose the Philosopher's Stone from one of several "grand discoveries" they can make, allowing them to make one per month.

Video Games

 * In Operator's Side/Lifeline, this is what drives the whole plot of the game.
 * In Golden Sun: Dark Dawn, it is revealed that the Wise One is a Philosopher's Stone. Apparently, in this world, Philospher's Stones are extremely powerful and intelligent beings forged through Alchemy.
 * In Castlevania: Lament of Innocence, there is brief mention of Alchemists' quest for the Philosopher's Stone leading them to create the Black Stone and Crimson Stone, both of which are less helpful to humans and extremely useful to vampires (one casts eternal night on the surrounding area, the other allows one to gain power from stealing the souls of others, but turns the user into a vampire). This is presumably intended to explain Dracula's mad h4x, as.
 * Valkyrie Profile the Philosopher's Stone takes the form of the Great Big Book of Everything. It allows the sorcerer Lezard Valeth to look up and know just about any bit of lost information and in the end allows him to survive Ragnarok.
 * In League of Legends it's a low level item that increases health and mana regeneration and earns gold.

Web Original

 * The defunct adoptables website Valenth featured the Fatis Mirajin, a Philosopher's Stone Gone Horribly Wrong. Accidentally created by a young elven alchemist in the site's backstory, it turned out to have a very dangerous flaw: corrupting elemental dream energy and horribly mutating anything that came near it. One of the main plot threads of the site was the fact that it is now threatening to turn the whole world into Dream Land.

Western Animation

 * The Philosopher's Stone appeared in an episode of The Real Adventures of Jonny Quest. The villain greedily used the stone's power to make himself rich, and in consequence lost his soul. This prevented him from using it to make more gold, so he got around that limitation by kidnapping Hadji and forcing him to make gold to keep his friends alive.
 * The Philosopher's Stone made an appearance in an episode of the Aladdin series. In it, it was the source of all mystical power in the cosmos. The evil wizard Mozenrath created one with the aid of the wizard trapped in a book, Khartoum, only for Khartoum to double cross him and use the stone to escape the book and become the most powerful wizard in the world. However, while the stone's power was limitless, due to it growing unchecked, it exploded.
 * One of the reasons Gargamel pursues The Smurfs is that the Smurfs are the Philosopher's Stone. At least six Smurfs are needed to make gold.