One of the recurring plot lines is the relationship between Leonard and Penny. Leonard becomes attracted to Penny in the pilot episode and his need to do favors for her is a frequent point of humor in the first season. Meanwhile, Penny dates a series of muscular, attractive, unintelligent, and insensitive jocks. Their first long-term relationship begins when Leonard returns from a three-month expedition to the North Pole in the season 3 premiere. However, when Leonard tells Penny that he loves her, she realizes she cannot say it back. Both Leonard and Penny go on to date other people; most notably with Leonard dating Raj's sister Priya for much of season 4. This relationship is jeopardized when Leonard comes to falsely believe that Raj has slept with Penny, and ultimately ends when Priya sleeps with a former boyfriend in "The Good Guy Fluctuation".
Amy and Howard begin collaborating on a neuroprosthetics project, upsetting Sheldon and Raj, who feel they are not spending as much time with them. When they seek solace with an annoyed Bernadette, she exploits the situation to trick Sheldon into doing Howard's chores. Penny successfully employs the approaches recommended in one of Bernadette's parenting books to deal with Sheldon, but Leonard believes she is coddling Sheldon too much. Sheldon and Raj resolve the issue of missing their significant others by spending time together.