Holly, Barney, Dan and Mel all left before the series began. Several new characters were introduced in the first episode: staff nurse Dillon Cahill (Dan Rymer), ambulance technician Nicki Marshall (Kelly Harrison) and paramedic "Comfort" (Martina Laird). Later on the team were joined by SHO Lara Stone (Christine Stephen-Daly) and Chief Executive Jan (Judy Loe). Jack's brother Tony (Lee Warburton), was later taken on as a security guard after several incidents persuaded Jan to increase security in the department.
Max was suspended after supplying methadone to his fiancée Amanda's son. The locum brought in to replace him, Philippa, was hopeless, and eventually resigned after making a fatal mistake. Max was later reinstated.
Later in the series, Chloe left, fleeing the country to escape from the police.
Patrick, about to leave to take a consultant's post in London, was involved in an RTA, and died after saving the lives of several teenagers. Dr. Simon Kaminski (Christopher Colquhoun) came to take his place. Student nurse Roxanne Bird (Loo Brealey) also joined the team.
Jan came under fire from the press after a virus in the hospital caused A&E to be overfull for days. When an MP's son died in a corridor, there were calls for Jan's resignation. Jan, however, leaked Max's past to the papers, and as Max had made the decision not to ventilate the MP's son, the papers latched onto him, naming him 'Doctor Drugs'. The board told Max to take 'gardening leave', whereupon Max resigned. Max's replacement was Harry Harper (Simon MacCorkingdale).
The series ended with Nikki and Fin being badly injured whilst on a shout, and the team had to fight to save Nikki's life. And as she lay unconscious, another shock was in store - Lara was arrested after the policeman who had tried to rape her died from the injuries she caused.