The article is a narrative review of the theoretical standing and empirical evidence for the cognitive behavioural model of medically unexplained symptoms (MUS) in general and for chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS) in particular. A literature search of Medline and Psychinfo from 1966 to the present day was conducted using MUS and related terms as search terms. All relevant articles were reviewed. The search was then limited in stages, by cognitive behavioural therapy (CBT), condition, treatment and type of trial. Evidence was found for genetic, neurological, psychophysiological, immunological, personality, attentional, attributional, affective, behavioural, social and inter-personal factors in the onset and maintenance of MUS. The evidence for the contribution of individual factors, and their autopoietic interaction in MUS (as hypothesised by the cognitive behavioural model) is examined. The evidence from the treatment trials of cognitive behavioural therapy for MUS, CFS and IBS is reviewed as an experimental test of the cognitive behavioural models. We conclude that a broadly conceptualized cognitive behavioural model of MUS suggests a novel and plausible mechanism of symptom generation and has heuristic value. We offer suggestions for further research.