The Big Bang Theory/Tear Jerker

Season One

 * Leonard's Despair Event Horizon in "The Nerdvanna Annihilation" over Penny's anger-induced jabs of the four's lifestyle.

Season Two

 * Leonard's Hilariously Abusive Childhood is, like Amy's past, funny but sad. For instance, he never had a birthday party as a kid, and he essentially had to give up his childhood to become the genius he is now. Poor guy.
 * "The Maternal Capacitance" is one long episode designed to make you cry for Leonard. Poor guy with a mother like that, for so long... he actually built a hugging machine because there was such a lack of affection in his house.
 * His father used to borrow it...
 * His mother's effect on Penny is quite a tearjearker in it's own right.
 * In "The Friendship Algorithm", Sheldon is at a bookstore looking for a book about making friends when he strikes up a conversation with a little girl. They get along, with Sheldon offering to take her to a zoo before Leonard drags him away because of how bad it looks. It's set up as a CMOF and it is, but it also fits here because we (the audience) know, for all his quirks and annoying habits, would never do something like that to her and was probably relatively safe with him. Child abduction and abuse are horrible, it's just people have to assume the worst even from someone who wouldn't even have a sexual encounter with a willing woman his age (Amy, Season 5). The absolute worse part: Sheldon was trying to learn how to make friends and that girl probably would've been a close friend (It's Sheldon, would it have been weirder than half the stuff he does?)
 * Really, it was sad not because of the specific events but because it once again showcased that on an emotional level Sheldon isn't much older than that girl, which has been the source of most of the problems in his life.
 * In the season finale, when Penny quietly admits to herself that she wishes Leonard wasn't going away for the whole summer to the North Pole.

Season Three
"Sheldon: (Reading) "Roommates agree that Friday nights should be reserved for watching Joss Whedon's brilliant new series Firefly". Leonard: Does that really need to be in the agreement?. Sheldon: Might as well settle it now, it's gonna be on for years."
 * Sheldon's meltdown in "The Guitarist Amplification."
 * Combined with Shout-Out and maybe a little Take That. C'mon, you know you shed a little tear with this dialog, when Leonard and Sheldon are signing the Roommates Agreements:


 * While it's still Played for Laughs, hearing Leonard's voice waver before he breaks down while talking about his mother in "The Pants Alternative" definitely counts.
 * Leonard and Penny breaking up, Leonard's heartbreak was devestating to watch, that what we heard about how hard he was taking it from Sheldon.

Season Four
"Penny: Wait, you've never been to a sleepover? Amy: No, unless you count the time I had influenza and shared a hospital room with a little Vietnamese girl... She didn't make it through the night, but up till then it was kinda fun."
 * Sheldon's Star Trek-based fanscript in "The Thespian Complex," with him leaving his mother to go to the future and Penny insisted on reversing the roles (She would play Spock and Sheldon would play his mother). Sheldon's script was based on the idea that nobody appreciated him or his intelligence, but portraying his mother made him realize how much his mother loved him. Of course, this isn't stated out loud but in Sheldon having an emotional breakdown playing both his mother and his ten year old self.
 * Whenever Amy's childhood is revealed, it's funny but usually kinda sad. For instance:

"Penny: (choked up) Give her the corsage Leonard."
 * And in S5E2, when she pleads to Penny, "No, I'm sorry, please don't cut me out of your life!"
 * In Season 5, she revealed that her cousin was paid off to go with her to junior prom, and he instead spent the money on drugs...

Season Five

 * Brent Spiner  is kind of cruel when you think about it.
 * Amy's isolation in "The Isolation Permutation" rings true, especially since her interactions with Penny made her estactic to be friends with a cheerleader type and to be excluded at all brings back ALL those painful memories.
 * Her comparing herself to a brain tumor is painfully unfunny.
 * In "The Ornithophobia Diffusion," Sheldon has a fear of birds and a blue jay lands on the apartment windowsill. The blue jay flies in and Sheldon, with the help of Bernadette and Amy, manages to overcome his fear. In the midst of just falling in love with the bird (calling it Lovey Dovey despite not being a dove) he opens the window and the blue jay flies out.
 * In the Stephen Hawking episode, Sheldon has to do tasks for Howard, who is helping him with his wheelchair. When Bernadette gets Sheldon to go dress shopping with Howard's mother. When Sheldon points out that her weight makes it hard for her to find a good dress she breaks down saying that she was quite a looker until she ate all the candy she received as gifts from her dates, leading to the start of her weight issues and makes him hold her. For a loud, annoying Jewish Mother, that really was depressing.