Challenging behaviour in patients with intellectual disability may be caused by physical, psychological and environmental factors. In 3 case histories, a multidisciplinary assessment in diagnosis and treatment is shown to be needed. A 48-year-old man with mild intellectual disability presented with cognitive deterioration, aggressive behaviour and physical symptoms. The diagnosis was mood disorder and dissociative symptoms. His functioning improved during and after treatment with psychotropic drugs and non-verbal psychotherapy. A 10-year-old girl with moderate intellectual disability who presented with temper tantrums was diagnosed as having no psychiatric disorder, but symptoms caused by environmental factors. After proper support and education for the parents, the patient's challenging behaviour disappeared. A 61-year-old woman with Down syndrome and Alzheimer's dementia presented with screaming, restlessness, struggling during daily care, and confusion. She was prescribed haloperidol and oxazepam and the screaming behaviour decreased. However, she kept on struggling while being cared for and was restless while sitting in her wheelchair. After a proper medical examination it appeared that the problem behaviour was caused by collapsed vertebrae and osteoporosis.