Since Howard lived with his mom for the most part of The Big Bang Theory, Mrs. Wolowitz is a regular member of the show's cast despite never appearing physically. Her existence is only established via her signature voice and consistent references from Howard. In The Big Bang Theory season 8 "The Comic Book Regeneration," Howard gets a phone call from his aunt revealing that his mom has passed away. Subsequently, the Pasadena gang comes in to support their friend; even Sheldon offers words of comfort. Mrs. Wolowitz's death is motivated by the real-life death of Carol Ann Susi, who provided the voice for the character.
In The Big Bang Theory season 10, "The Hot Tub Contamination," Sheldon finally reveals the origins of his weird three-knock rule. Surprisingly, the habit has rather dark origins as the socially inept genius started doing it after he walked in on George having sexual relations with another woman in his parents' bedroom. As a way to ensure that it would never happen again, Sheldon has started knocking three times to give anyone on the other side of the door the time to make sure that they are presentable before he comes in.
While the rest of the Pasadena gang throws Sheldon a birthday bash in The Big Bang Theory season 9, "The Celebration Experimentation," the socially inept genius gets overwhelmed and hides in the bathroom. Penny volunteers to talk him out to comfort him, and the result is arguably one of the most beautiful conversations between the friends. As Sheldon opens up about not really liking his birthday, Penny patiently reminds him that he is loved by his friends. She personally confesses that he is one of his favorite people in the world, despite their idiosyncrasies.
As the most romantic member of the Pasadena gang, Raj also happens to have the most tragic love life among the main cast of The Big Bang Theory. Over the years, he has had his fair share of break-ups, and every single time something goes wrong with his relationships, he takes a bit too hard. The Big Bang Theory often plays this up as humorous, but it's difficult not to feel bad for him after seeing him having a total meltdown in "The Monster Isolation" after Lucy runs out on him. Raj's eventual The Big Bang Theory finale fate makes it sadder.
By the time Amy and Sheldon get married in The Big Bang Theory season 11, weddings are no longer new to the show. Howard and Bernadette, and then Penny and Leonard tied the knot in previous seasons. That being said, there is something emotional about seeing two of the most emotionally challenged and socially awkward characters on the sitcom find love. Sheldon's emotional vow adds to the event's emotionality, considering that he is notoriously known to have an aversion to expressing his feelings.
Beverly and Leonard's relationship is one of the trickiest dynamics in The Big Bang Theory. Unlike Sheldon's bond with Mary, the Hofstadters' connection is tumultuous, to say the least. While Leonard does everything to ensure that his mother is proud of him, Beverly seems to be committed to keeping their relationship cold and problematic. In The Big Bang Theory season 12 "The Maternal Conclusion," however, Beverly finally realizes the error of her ways and asks her son's forgiveness for the horrible way he treated him over the years. This results in the pair finally patching things up.
As the inaugural couple, the sitcom devoted its early years to crafting Penny and Leonard's The Big Bang Theory love story. They have had several failed proposals, but in "The Gorilla Dissolution," they finally get engaged in the most unexpected way. After getting fired from Serial Apeist 2, Penny casually floats the idea of getting married. They start to bicker about the real reason that she wants to get married until she confesses that being booted from the job made her realize that she only needs Leonard to be happy, which quickly turns the moment into one of the most romantic scenes in The Big Bang Theory.
Unlike Missy and Mary, who have been introduced in The Big Bang Theory in season 1, Georgie waits until season 11's "The Sibling Realignment" to appear. However, his reunion with Sheldon is anything but great. As it turns out, the brothers had a falling out many years ago after the socially inept genius failed to appreciate all his brother's sacrifices. Following an intense argument, however, Sheldon realizes the error of his ways. Not only does he apologize for his misgivings, but he also thanks Georgie for everything he has done for their family.
In its one-time crossover with Young Sheldon, The Big Bang Theory finds a way to feature Sheldon's dad in the mothership series despite being dead for years before its events. As Sheldon struggles with the failure of his Nobel Prize in Physics bid, he comes across his dad's old football team pep speech, which perks him up. After spending years bad-mouthing his dad in The Big Bang Theory, seeing Sheldon watch his dad on the screen and realizing just how much he misses him is both touching and heartbreaking.
Sheldon has a deep connection with Professor Proton that is rooted back to his childhood. So when the fictional on-TV personality dies in The Big Bang Theory season 7 "The Proton Transmogrification," he is overcome with grief. Instead of processing his emotions healthily, however, he decides to pretend that losing Arthur Jeffries doesn't make him sad. Leonard knows better, however, than to believe him, but he doesn't push his best friend to open up, opting to wait for him until he is ready to open up. This highlights just how much Leonard knows his roommate, and how lucky Sheldon is to have someone like Leonard as his best friend.