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".
After Sheldon reminds the guys about the time they mined Bitcoin without him, the guys go on a quest to find their suddenly valuable missing cryptocurrency. They realize the currency is on a laptop which Leonard gave to Penny when they dating, which she then gave to her ex-boyfriend Zack. After Leonard and Penny go to Zack's apartment, he shows them a seven-year-old video that Penny recorded on the laptop soon after she broke up with Leonard. Leonard is touched by the video which shows a drunk Penny lamenting the break-up of her relationship with him.
Showrunner Steve Molaro, who took over from Bill Prady with the sixth season, credits some of the show's success to the sitcom's exposure in off-network syndication, particularly on TBS, while Michael Schneider of TV Guide attributes it to the timeslot move two seasons earlier. Chuck Lorre and CBS Entertainment president Nina Tassler also credit the success to the influence of Molaro, in particular the deepening exploration of the firmly established regular characters and their interpersonal relationships, such as the on-again, off-again relationship between Leonard and Penny. Throughout much of the 2012–13 season, The Big Bang Theory placed first in all of syndication ratings, receiving formidable competition from only Judge Judy and Wheel of Fortune (first-run syndication programs). By the end of the 2012–13 television season, The Big Bang Theory had dethroned Judge Judy as the ratings leader in all of syndicated programming with 7.1, Judy descending to second place for that season with a 7.0. The Big Bang Theory did not place first in syndication ratings for the 2013–14 television season, beaten out by Judge Judy.
Howard dresses as Sheldon for Halloween at work, hurting Sheldon's feelings. When Howard does not apologize, Amy and Sheldon dress as Bernadette and Howard at Penny and Leonard's party, angering Bernadette. Sheldon and Bernadette later bond over their painful childhood memories. Leonard is upset that Penny does not seem to remember that their first kiss was on Halloween. Penny later admits she does remember, but does not like to think of their first kiss as an unromantic drunken hookup. She likes to imagine their first kiss was one they shared on Leonard's birthday, which pleases him.
Kaley Cuoco as Penny: An aspiring actress from Omaha, Nebraska. Penny moves in across the hall from Sheldon and Leonard. She waits tables and occasionally tends the bar at the Cheesecake Factory. After giving up hope of becoming a successful actress, Penny becomes a pharmaceutical sales representative. Penny becomes friends with Bernadette and Amy, and they often hang out in each other's apartments. Penny and Leonard form a relationship and eventually marry.
When Amy sees Sheldon obsessively tying and untying his bow tie the day before their wedding, Amy tells him it doesn't need to be even because sometimes a little asymmetry looks good. On the day of the wedding, Sheldon stops his mother from trying to straighten his bow tie, saying it's supposed to be a little asymmetrical. When Mary comments that sometimes it’s the imperfect stuff that makes things perfect, Sheldon has a flash of inspiration and rushes to see Amy. Sheldon and Amy’s wedding is delayed as they excitedly work on a new theory of “super asymmetry”.
When Raj misses out on a job at the planetarium, his father says he has no confidence because Howard always makes fun of him. Raj distances himself from Howard and later gets the job. Howard is hurt by this (even after apologizing to him) and tries to make amends with Raj after his first performance at the planetarium but, when he sees him get a date, he leaves without speaking to him, thinking that the latter's life is better without him. Meanwhile, Sheldon and Amy try randomly dividing up wedding tasks, but they keep arguing. The only thing they can agree on is to get married, so they decide to just get married at City Hall. However, Sheldon decides that he wants a first dance with his new wife and they go home to plan their wedding.