The show originally focused on put-upon "nice guy" Leonard (Johnny Galecki in a much less appealing role than David on Roseanne) and his attempts to date the much cooler but airheaded aspiring actress next door, Penny (Kaley Cuoco). The show quickly realized its fan favorite character was Leonard's irritable roommate, Sheldon (Jim Parsons), and basically ran with it. Nowadays, with the welcome addition of female brains (and the gradual geekifying of Penny), the show basically follows the formula of a group of six friends, some of whom are coupled, all of whom are nerds.
Key Episodes
1.4 "The Luminous Fish Effect": Sheldon darts manically from project to project after he is fired, prompting Leonard to call in the big guns: Sheldon's mother (Laurie Metcalf, another Roseanne alum). I love Metcalf's warm performance as a Christian mom full of homespun wisdom, and it's fun to learn about Sheldon's surprisingly down-to-earth background.
1.6 "The Middle-Earth Paradigm": Leonard and Sheldon fundamentally misunderstand Penny's invitation to her Halloween party, asking about the costume parade, etc. Leonard is proud of his Frodo costume until he meets Penny's musclebound ex-boyfriend. After he leaves, humiliated, Penny follows him and gives him a drunken kiss, in the first actual sign that Penny is interested in Leonard and it's not just going to be a weird unrequited thing forever. Even though it mostly is.
3.23 "The Lunar Excitation": Howard (Simon Helberg) and Raj (Kunal Nayyar) create an online dating profile for Sheldon, and everyone is surprised when it turns up a perfect match--the equally nerdy Amy Farrah Fowler (Mayim Byalik, TV's Blossom). Bialik's performance is delightful and her addition to the show really kicks things up in the next few seasons. Meanwhile there is some other business with Penny and Leonard, as usual.
Bonus Episodes
1.5 "The Hamburger Postulate": Leonard is used for casual sex by his ex, the extremely logical Sheldon rival Leslie Winkle (Sara Gilbert, in another bit of amusing Roseanne reunionry).
1.11 "The Pancake Batter Anomaly": The guys get sick and Penny takes care of them; a standard sitcom plot notable for the first signs of a surprising amount of warmth between Penny and Sheldon.
1.17 "The Tangerine Factor" & 2.1 "The Bad Fish Paradigm": A two-part episode flirts with the idea of putting Leonard and Penny together, but although they enjoy dating briefly, Penny is hurt when Leonard says she isn't smart.
2.8 "The Lizard-Spock Expansion": Leonard has a relationship with a non-Penny woman, a likeable doctor (Sara Rue), and Sheldon comes up with an expanded version Rock-Paper-Scissors.
2.11 "The Bath Item Gift Hypothesis": Sheldon goes nuts trying to think of a Christmas present for Penny, and Penny gets him the perfect one. Am I Sheldon/Penny shipper? Should I be?
2.15 "The Maternal Capacitance": Leonard's mother turns out to be the kind of brilliant, cold, neglectful scientist that we all expected Sheldon's mother to be, which sort of explains a lot about why Leonard is so subtly messed up.
3.1 "The Electric Can Opener Fluctuation": The guys return from an arctic expedition from the end of season 2 (don't worry about it), and Penny and Leonard get together.
3.5 "The Creepy Candy Coating Corrollary": One of the things TBBT likes to do is to have geeky guest starts. In this episode, Sheldon sparks up a rivalry with Wil Wheaton. In another important deveopment, Penny introduces Howard to a friend, Bernadette (Melissa Rauch), who will become a major character, and sleazy Howard's first real girlfriend.
3.6 "The Cornhusker Vortex": I'm including this episode with Raj and Howard flying kites together because I remember it being pretty gay. Raj/Howard is second only to Sheldon/Penny in the fanfic grand prix.
3.9 "The Vengeance Formulation": Howard tries to decide between Bernadette and all the other theoretical girls he might like, including Battlestar Galactica's Katee Sackhoff, who appears in a fantasy sequence.
3.19 "The Wheaton Recurrence": Penny and Leonard break up because Penny can't say "I love you" and something to do with Wil Wheaton.
4.10 "The Alien Parasite Hypothesis": On a girls' night out, Amy Farrah Fowler develops a crush on Penny's ex, which leaves her flustered and overanalytical. Here, Amy, introduced as the female Sheldon, begins developing her own traits, notably her libido, which more-or-less-asexual Sheldon definitely doesn't share.
4.20 "The Herb Garden Germination": Sheldon and Amy's experiment in gossip results in the reveal that Howard and Bernadette are engaged.
And now it's season five.
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