Sheldon's mother Mary refuses to attend his wedding unless he invites his older brother George, with whom he is no longer speaking. Sheldon and Leonard fly to Texas to talk to George, who now owns a chain of tire stores. He refuses to attend and later explains to Leonard and Sheldon that the family sacrificed a lot to fund Sheldon's education, and he was stuck caring for their mother and sister Missy after their father died while Sheldon was in college. Sheldon never thanked him for this. Leonard takes George back to the hotel room where Sheldon apologizes for what he did and the brothers reconcile. George agrees to attend the wedding. Meanwhile, Howard and Bernadette's children contract pinkeye, infecting everyone except Penny, much to Amy's fury.
In November 2016, it was reported that CBS was in negotiations to create a spin-off of The Big Bang Theory centered on Sheldon as a young boy. The prequel series, described as "a Malcolm in the Middle-esque single-camera family comedy" would be executive-produced by Lorre and Molaro, with Prady expected to be involved in some capacity, and intended to air in the 2017–18 season alongside The Big Bang Theory. The initial idea for the series came from Parsons, who passed it along to The Big Bang Theory producers. In early March 2017, Iain Armitage was cast as the younger Sheldon, as well as Zoe Perry as his mother, Mary Cooper. Perry is the real-life daughter of Laurie Metcalf, who portrays Mary Cooper on The Big Bang Theory.
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.
Although the original pilot was not picked up, its creators were given an opportunity to retool it and produce a second pilot. They brought in the remaining cast and retooled the show to its final format. Katie was replaced by Penny (Kaley Cuoco). The original unaired pilot has never been officially released, but it has circulated on the Internet. On the evolution of the show, Chuck Lorre said, "We did the 'Big Bang Pilot' about two and a half years ago, and it sucked ... but there were two remarkable things that worked perfectly, and that was Johnny and Jim. We rewrote the thing entirely and then we were blessed with Kaley and Simon and Kunal." As to whether the world will ever see the original pilot on a future DVD release, Lorre said, "Wow, that would be something. We will see. Show your failures..."
After the strike ended, the show was picked up for a second season, airing in the 2008–2009 season, premiering in the same time slot on September 22, 2008. With increasing ratings, the show received a two-year renewal through the 2010–11 season in 2009. In 2011, the show was picked up for three more seasons. In March 2014, the show was renewed again for three more years through the 2016–17 season. This marked the second time the series gained a three-year renewal. In March 2017, the series was renewed for two additional seasons, bringing its total to 12, and running through the 2018–19 television season.
After learning Sheldon went behind their backs to work with the military again, Leonard and Howard say Sheldon is like Thomas Edison, taking credit for others' ideas, while they are more like Nikola Tesla. Leonard and Howard bring in Barry Kripke to help create a better idea than Sheldon's, but Kripke goes to the military himself, cutting all three of them out. Meanwhile, Bernadette fears Ruchi is trying to steal her projects at work while she is on maternity leave and enlists Raj to spy on her. Though he finds proof that Ruchi may be stealing from Bernadette, Raj tries to defend Ruchi like a boyfriend would, pointing out Bernadette's hypocrisy as she would most likely have stolen from other people's projects as well. Ruchi is not happy about this and promptly dumps Raj.
The show made its United Kingdom debut on Channel 4 on February 14, 2008. The show was also shown as a 'first-look' on Channel 4's digital offshoot E4 prior to the main channel's airing. While the show's ratings were not deemed strong enough for the main channel, they were considered the opposite for E4. For each following season, all episodes were shown first-run on E4, with episodes only aired on the main channel in a repeat capacity, usually on a weekend morning. From the third season, the show aired in two parts, being split so that it could air new episodes for longer throughout the year. This was due to rising ratings. The first part began airing on December 17, 2009, at 9:00 p.m. while the second part, containing the remaining eleven episodes, began airing in the same time period from May 6, 2010. The first half of the fourth season began airing on November 4, 2010, at 9:00 p.m., drawing 877,000 viewers, with a further 256,000 watching on the E4+1 hour service. This gave the show an overall total of 1.13 million viewers, making it E4's most-watched programme for that week. The increased ratings continued over subsequent weeks.
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.