Grey's Anatomy first permiered on March 27, 2005, and concluded on May 22, 2005, and consist of only nine episodes, making it the shortest season to date. The first season introduces the main character, Meredith Grey, as she enrolls in Seattle Grace Hospital's internship program and faces unexpected challenges and surprises. Season one had nine series regulars, three of whom have been part of the main cast ever since.

Patrick Dempsey, who portrayed Derek, decided to leave the series because the work schedule was too time-consuming and didn't allow him to spend time with his family. Derek's death was partly due to claims of Dempsey causing disruptions on set and feeling done with the show.

However, this didn't sit well with Grey's Anatomy's showrunner Shonda Rhimes who decided to drop her after branding her as “difficult to work with”. This wasn't the only reason by the way, as there had been instances where Katherine Heigl publicly criticized the show because of its absurd filming hours.