Mental retardation involves an impairment of intellect and learning ability of congenital origin. Causes may be genetic or environmental and have major implications for preventive medical practice and the ethical behaviour of health professionals. The relevance to psychiatry is the demonstration of how brain function can be affected by various congenital factors, how these may make psychiatric illness more likely, example, through epilepsy, and the impact on family function. This chapter explores case histories based on mental retardation. The classical chromosomal cause of mental retardation is Down's syndrome, first described by Dr Langdon Down's in 1866. The syndrome is usually caused by trisomy 21, but rarely may be due to a translocation. The organic brain abnormalities that underlie mental retardation also predispose to epilepsy and to psychiatric illness. Various organic processes can overlie the original mental retardation. Cognitive decline in a Down's person must raise the suspicion of a superimposed dementia.