Background Challenging behaviour is a major problem among people with intellectual disabilities. Physical factors may be an important cause. The aim of the present systematic review was to determine the physical conditions associated with challenging behaviour. Methods A literature search was conducted in PubMed and the Cochrane systematic review database for empirical studies published between 1990 and 2008. The quality of all the studies that met the inclusion criteria was assessed using the SIGN-50 methodology checklists. Results The search identified 45 studies, which looked at general medical conditions, motor impairment, epilepsy, sensory impairment, gastrointestinal disease, sleep disorders, dementia and others. There were four high-quality observational studies, seven well-conducted observational studies, 21 observational studies of low methodological quality and 13 non-analytical studies. There were significant and independent associations between challenging behaviours and urinary incontinence, pain related to cerebral palsy and chronic sleep problems, and between self-injurious behaviour and visual impairment. No association was found with hearing impairment, bowel incontinence, mobility impairment or epilepsy. Many other physical conditions were not addressed at all. Conclusion Medical conditions can play a role in challenging behaviour, and this should be evaluated in the clinical setting. So far, the level of evidence is generally low, and longitudinal studies are completely lacking. We recommend a systematic approach to research examining the role of physical conditions in challenging behaviour, the ultimate aim being to establish a basis for the development of clinical guidelines.