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In Season 1, Penny moves in across the hall from Sheldon and Leonard. She befriends her neighbors as well as Howard and Raj. Leonard briefly dates Leslie Winkle. Raj learns that he can talk to women when he drinks alcohol. Penny breaks up with her boyfriend and agrees to go on a date with Leonard.

In Season 2, Leonard and Penny go separate ways. Instead, Leonard starts seeing Stephanie Barnett and Penny goes on a date with Stuart. At the end of the season, the guys prepare for an expedition to the North Pole.

In Season 3, Penny is excited to welcome Leonard back from the North Pole. Leonard and Penny begin to date. Howard asks Leonard to set up a blind date for him with one of Penny's friends. Sheldon meets Wil Wheaton. Howard and Bernadette begin to date but Howard has doubts. Penny breaks up with Leonard after feeling pressured into saying "I love you". Howard and Raj find an online dating match for Sheldon.

In Season 4, Sheldon goes on a date with Amy and after their break-up buys twenty-five cats. Leonard hooks up with Raj's sister. Amy joins Penny and Bernadette's girls' night. Priya tells Leonard to stop being friends with Penny while they're dating. Bernadette considers breaking up with Howard. Instead, they become engaged. Bernadette receives her doctorate.

In Season 5, Penny and Raj spend a night together. Leonard and Priya are in a long-distance relationship. Raj dates a gold-digging deaf girl from Penny's spin class. Sheldon and Wil become friends. Amy becomes Bernadette's maid of honor. Sheldon accepts a more serious relationship with Amy. Leonard and Penny begin dating secretly. Howard becomes an astronaut. Bernadette and Howard marry before he goes to space.

In Season 6, Penny has doubts about her relationship with Leonard. Howard is homesick but once back on Earth cannot stop talking about his trip to space. Raj dates Lucy. Leonard is asked on an expedition to the North Sea.

In Season 7, Raj and Lucy break up. Leonard returns to Pasadena. Amy takes a job at Caltech. Penny realizes she is married to Zach. Penny quits her job to focus exclusively on acting. Howard is offered another chance to go to space. Penny and Leonard get engaged.

In Season 8, Penny interviews for a position as a pharmaceutical sales rep with Bernadette's company. Sheldon becomes a Junior Professor. Raj dates Emily. Howard's mother dies. Howard meets his half-brother. Sheldon's and Leonard's mothers meet. Penny and Leonard cannot set a wedding date.

In Season 9, Penny and Leonard elope. Amy pauses her relationship with Sheldon. Amy dates Dave. Sheldon makes an effort to win Amy back. Raj has to choose between Emily and Claire. Bernadette is pregnant.