The twenty-first series of the British medical drama television series Holby City began Airing on BBC One on 2 January 2019 in the United Kingdom. The series consists of 53 episodes. Kate Hall acts as the series producer for episode one and was replaced by Jane Wallbank from the following episode; Simon Harper is the executive producer. The series is billed as an anniversary year for the drama as it celebrates twenty years since its launch. The series also features a crossover episode with sister show Casualty, an episode written by the show's co-creator Tony McHale and the show's 1000th episode, due to be broadcast in November 2019. Thirteen actors reprise their roles from the previous series and former cast members return for guest stints throughout the series. Three new regular characters were also introduced, while Nic Jackman was promoted to the main cast in his role as foundation doctor Cameron Dunn.

The twentieth series of the British medical drama television series Holby City began airing on BBC One in the United Kingdom on 2 January 2018, and concluded on 27 December 2018. The series consists of 52 episodes; a decrease from the previous series. Kate Hall serves as the series producer, while Simon Harper continued his role as the executive producer. Fifteen cast members reprised their roles from the previous series. Four actors departed during the series, including long-standing cast member James Anderson. Catherine Russell reprised her role as Serena Campbell from episode six. Throughout the series, multiple characters returned for guest stints, including Zosia March, Bernie Wolfe and Mo Effanga.