Howard: How's Sheldon doing with Amy gone?
Leonard: Well, the last three nights I've had to take him to get a haircut, to the train store, and to a Walgreens in Arcadia where they still have the "good ibuprofen." Now, ask me how I'm doing with Amy gone.
Raj: How are you doing with-
Leonard: Shut up.

Sheldon: This song is never going to stop. Have you ever dealt with something so relentlessly irritating?
Leonard: That's a trick question, right?

Leonard: What would you be if you were attached to another object by an inclined plane, wrapped helically around an axis?
Sheldon: Screwed?
Leonard: There you go.

Professor Proton: Can I ask you a question?
Leonard: Yeah, sure.
Professor Proton: Why do you put up with Sheldon?
Leonard: Oh, you know because we're friends.
Professor Proton: Why?
Leonard: Wow, you ask really hard questions. Look, I know he can be aggravating, but what you have to remember is he's not doing it on purpose, it's just how he is. But he's also loyal and trustworthy and we have fun together.
Professor Proton: You know you're describing a dog?
Leonard: He did bite me once. But in his defense, I came up behind him while he was eating.
Professor Proton: They hate that.
Leonard: Sheldon is the smartest person I have met. He's a little broken and he needs me. And I guess I need him too.
Professor Proton: Why is that?
Leonard: Boy, you will not let this go, will you?

Amy: I gave you one job! Keep an eye on him. How hard is that?

Sheldon: Because there's only one of me, I'm more valuable.
Penny: Right.
Sheldon: Although, Amy's already taken me out of my package and played with me.

Amy: Why didn't you tell me?
Bernadette: We didn't want you to worry.
Amy: Should I worry?
Penny: No, come on, it's Sheldon. Nothing is gonna happen.
Amy: That's what you said to me when I started dating him. And then five years later, bingo-bango, something happened.