Melissa Rauch as Bernadette Rostenkowski-Wolowitz (recurring season 3, starring seasons 4–12):[51] 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.
Laura Spencer as Emily Sweeney (recurring seasons 7–8, 10, starring season 9):[55] A dermatologist at Huntington Hospital. Emily went to Harvard and delights in the macabre and states that she likes her job because she can cut things with knives. Prior to meeting Raj, Emily was set up on a blind date with Howard. After finding Emily's online dating profile, Raj has Amy contact her as his wingman instead. Their relationship becomes exclusive, but Raj later breaks up with Emily when he becomes infatuated with the bartender Claire (Alessandra Torresani).

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.
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