In 2010, Leonard, Howard, and Raj mined a lot of Bitcoin, now worth thousands of dollars, but left Sheldon out due to his fear of tax implications. Flashbacks are shown of how the Bitcoin ended up on an old laptop of Leonard's, which Penny gave to her old boyfriend Zack after she and Leonard broke up. In 2017, Leonard and Penny retrieve the computer from Zack, who first shows them a video of a drunken Penny apologizing for breaking up with Leonard. The Bitcoin is not found on the laptop. Sheldon had moved it to a flash drive on Leonard's keychain to teach the guys a lesson, but Leonard lost the keychain years ago. A final flashback to 2013 shows Stuart discovering the flash drive, which he decides to erase and sell for $10.
Melissa Rauch as Bernadette Rostenkowski-Wolowitz (recurring season 3, starring seasons 4–12): A young woman who initially is a co-worker at The Cheesecake Factory with Penny to pay her way through graduate school, where she is studying microbiology. Bernadette is introduced to Howard by Penny; at first, they do not get along, apparently having nothing in common. They date and later get engaged and married. Although generally a sweet and good-natured person, Bernadette has a short fuse and can be vindictive and lash out when provoked.
Barry Kripke says that he can get proof that Pemberton plagiarized his thesis, which would destroy his chances at the Nobel Prize. Sheldon and Amy decide not to pursue this; they want to win on their own merits. Leonard decides to get the information from Kripke. Amy and Sheldon give it to Pemberton and Campbell, as they refuse to blackmail them. Campbell is furious that Pemberton's dishonesty could hurt his own career. It is revealed that Campbell is sleeping with Pemberton's ex-wife, causing the pair to brawl. Afterwards, Campbell exposes Pemberton, causing Pemberton to be fired. Amy and Sheldon reject a drunken Campbell's request to join their team. Bernadette tells Howard that another waitress at the Cheesecake Factory was attracted to him back in the day, so she said Howard had hepatitis to scare her off. Howard obsesses over who it was, until he tells Bernadette she is the only one that matters to him.
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".
Sheldon and Amy are surprised to find that Wil Wheaton's new Professor Proton show is actually very entertaining and that Wil had Howard on as a guest. On Howard's suggestion, Sheldon apologizes to Wil, mending their friendship, and tells him he wants to be on the show; but Wil asks for Amy. Sheldon tells her to do it, but she says she often doesn't do things to avoid upsetting him. Sheldon is horrified when he realises how selfish he has been, especially when he finds out that the men do the same for him. Sheldon encourages Amy to go on the show to inspire girls to pursue science while trying to control his obvious jealousy for her. Meanwhile, Leonard writes a book about a physicist that solves a murder, the protagonist Logan Dean is based on himself. Bernadette points out Logan's mean boss Illsa is similar to Penny, who thinks it is based on Bernadette, though Leonard does not correct her. However, Bernadette tells Penny the truth, upsetting her and making her mad at Leonard. After calling his mother for advice, Leonard learns that Illsa is actually like her; but abandons the book when he realizes he wrote romantic tension into the relationship between the characters.