Doctors is a British medical soap opera which began broadcasting on BBC One on 26 March 2000. Set in the fictional West Midlands town of Letherbridge, the soap follows the lives of the staff and patients of the Mill Health Centre, the Best Practice and Sutton Vale Surgery, three fictional NHS doctor's surgeries. The following is a list of characters that first appeared in Doctors in 2005 and 2006, by order of first appearance. All characters are introduced by the programme's executive producer, Will Trotter. Adrian Lewis Morgan debuted as Jimmi Clay in September 2005 and has gone on to be the longest-serving cast member on Doctors. He was followed by his wife, Amanda (Emma Samms). Jaye Griffiths joined in January 2006 as doctor Elizabeth Croft. Nick West (Michael McKell) then began appearing in March 2006. Receptionist Donna Parmar (Martha Howe-Douglas) then debuted in April 2006. Donnaleigh Bailey joined as nurse Michelle Corrigan in June 2006, who was followed by doctor Joe Fenton (Stephen Boxer) in September of that year, as well as Will Hurran (Joe McMullen). Additionally, multiple other characters appeared throughout the two years.

Dr. Jimmi Clay, portrayed by Adrian Lewis Morgan, first appeared on 5 September 2005. Having appeared continuously since, Morgan has gone on to become the programme's longest serving cast member. He joined the cast shortly after his role in Holby City had ended; he was a fan of the soap and was excited to audition for a regular part. Producers introduced the character's wife, Amanda (Emma Samms), shortly after his arrival, and he later established relationships with detective Eva Moore (Angela Lonsdale) and Cherry Malone (Sophie Abelson), the latter of whom he married.

After "a bit of a lull" regarding his storylines, Jimmi became the focus of a major storyline in 2019 which sees him wrongfully arrested and imprisoned for several months. Morgan was excited to be given the storyline as it felt different for himself and the soap itself. Morgan has received several award nominations for his portrayal of Jimmi, including Best Male Dramatic Performance at the British Soap Awards, and in 2020, he was announced as the winner of the Male Acting Performance award at the RTS Midlands Awards.

Amanda Vardalis (also Clay), portrayed by Emma Samms, initially appeared between 14 October and 9 December 2005, before returning for a brief stint from 27 April to 30 May 2018. Amanda was introduced as the older wife of Jimmi Clay (Adrian Lewis Morgan) and is a complementary therapist. Samms initially found the age difference between the two characters flattering until she learned that other characters were scripted to show their disbelief at Jimmi being married to an older woman. Jimmi and Amanda's marriage is strained upon Amanda's introduction; they allow each other to pursue other sexual affairs but Amanda is jealous of his emotional connection with Sarah Finch (Andrea Green). Amanda discovers a lump on her breast, and after Jimmi learns and pushes her to see a doctor, she is told that the lump is benign. However, she lies to Jimmi and says that the lump is cancerous for his attention and sympathy, attempting to push for them to move to California for specialist treatment. Sarah immediately suspects that Amanda is lying, and after he learns the truth, Jimmi is furious and leaves her.

Samms reprised the role in 2018 when Amanda returns to Letherbridge following the death of her recent husband. She said to Inside Soap that Amanda initially wants to see how Jimmi is doing and does not let him know she is back straight away. Samms explained: "Amanda is actually in a very desperate place, and she needs help." It eventually emerges that she is in a dispute with her dead husband's children over his will. Despite her success in American series following her exit, Samms "jumped at the chance" to return to Doctors since she enjoyed her initial stint on the soap, particularly working with Morgan. The producers promised Samms that she would be working with Morgan again, since he was the only cast member still in the series from her original stint. She also filmed scenes with Dido Miles, who portrays Emma Reid, who she said was "welcoming and absolutely delightful" and wished she could have filmed more scenes with.

Dr. Elizabeth Croft, portrayed by Jaye Griffiths, first appeared on 3 January 2006 and made her final appearance on 13 April 2006. Elizabeth was introduced to the Mill Health Centre as a doctor who had previously worked in poor parts of Asia. Due to her experiences there, Elizabeth is often shown to be short and up-front with patients who she sees to be wasting NHS time. On her BBC Online profile, Elizabeth was described as a "spiky, abrupt character" who cannot stand office politics, an example being her refusing to contribute to Faith Walker's (Eva Fontaine) birthday collection pot, until she later only puts a pound coin in. It also noted that she is "ambitious and uses her dark sense of humour to push herself forward".

Elizabeth is hired to replace Helen Thompson (Corrinne Wicks) and as soon as she begins working at the Mill, she immediately surprises and irritates her colleagues with how frank she is. Receptionist Sarah Finch (Andrea Green) becomes aggravated by Elizabeth since she criticises various practises at the surgery, as well as practice manager Julia McGuire (Diane Keen) taking a dislike to her. Elizabeth tries to cop herself a partnership as soon as she arrives, to Julia's annoyance. Mac McGuire (Christopher Timothy) assures her that he will think about it. After she has a brief fling with Nick West (Michael McKell), she becomes pregnant. She keeps the pregnancy a secret and soon has an abortion. However, Nick discovers the truth and he lashes out at Elizabeth after he learns of the abortion. Mac eventually offers Elizabeth a chance to go into partnership with him at the Mill, but not wanting to stay around Nick following his cruel reaction, she declines and leaves Letherbridge.

For her role as Elizabeth, Griffiths received a nomination for Sexiest Female at the 2006 British Soap Awards.