In the show, the song "Soft Kitty" was described by Sheldon as a song sung by his mother when he was ill. Its repeated use in the series popularized the song. A scene depicting the origin of the song in Sheldon's childhood is depicted in an episode of Young Sheldon, which aired on February 1, 2018. It shows Sheldon's mother Mary singing the song to her son, who is suffering with the flu.
Science has also interfered with the characters' romantic lives. Leslie breaks up with Leonard when he sides with Sheldon in his support for string theory rather than loop quantum gravity. When Leonard joins Sheldon, Raj, and Howard on a three-month Arctic research trip, it separates Leonard and Penny at a time when their relationship is budding. When Bernadette takes an interest in Leonard's work, it makes both Penny and Howard envious and results in Howard confronting Leonard, and Penny asking Sheldon to teach her physics. Sheldon and Amy also briefly end their relationship after an argument over which of their fields is superior.
Leonard gives an interview on public radio where he admits physics research might be at a dead end. The university is furious and, while trying to think of reasons to put in a retraction, he depresses Sheldon into thinking he might be right. Howard and Raj come over and end up just as depressed. Getting drunk with Penny, the men go to the grave of Richard Feynman and realize there is hope for physics as long as they believe in it. Leonard accidentally sends a drunken email to Human Resources. Meanwhile, Amy and Bernadette agree with each other to keep quiet about the success in their careers so as not to upset Sheldon and Howard. While bragging to each other, they end up arguing which of their fields is better.
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.
Getting called into Human Resources for Amy's outburst, Mrs. Davis tells her and Sheldon they are blowing their chances at the Nobel Prize. Amy would be the fourth woman to win in Physics, pressuring her to be a role model for women everywhere. To calm down, they try a sensory deprivation tank, which Sheldon loves, but Amy's mood only worsens. Sheldon does not know how to help and ends up holding her while singing "Soft Kitty". A newly confident Amy goes back to Human Resources to be allowed to campaign again and shares a drink with Mrs. Davis. Meanwhile, Howard buys a scooter to ride with Raj like in the old days. Bernadette finds out and makes him sell it since it's too dangerous. Bert buys it and ends up meeting a nurse after he dislocates his arm in a wreck.
In the season eight finale, Sheldon and Amy get into a fight about commitment on their fifth anniversary. Amy tells Sheldon that she needs to think about the future of their relationship, unaware that Sheldon was about to propose to her. Season nine sees Sheldon harassing Amy about making up her mind until she breaks up with him. Both struggle with singlehood and trying to be friends for the next few weeks until they reunite in episode ten and have sex for the first time on Amy's birthday.
When Mayim Bialik first learned she had to say goodbye to neurobiologist Amy Farrah Fowler, she opened up about the show ending in a blog post, asking, "And now I start to figure out what next. Where will life take me? Where will this career go? What do I want?" Up next she has a voice role in The Inspector Chronicles, a quasi-parody of Doctor Who making the leap from short to feature film. She'll reprise her role as the voice of the Inspector's time machine, known as B.O.O.T.H. Aside from that, she doesn't have any major projects lined up, aside from preparing to not see her close-knit cast the way she'd grown accustomed to. "We'll have to see what our lives look like," she told Us Weekly in early May about the chance they'll remain close. "I mean, we're all going to be on different schedules now; it's very different."