The prescription of psychotropics in mentally retarded subjects is complicated by both the complex neuropsychiatric diagnosis and the lack of systematic research with respect to efficacy, side effect profile and pharmacokinetic variables of current available compounds. In general, antipsychotics are widely prescribed for challenging behaviours. Preferably, a functional psychopharmacological strategy should be followed aimed at the induction of changes in symptomatology without influencing adaptive, social or cognitive functioning. In this respect, experiences are available with serotonin modulating compounds, opiate antagonists and mood stabilizing agents. Concerning pathogenetic principles, functional disturbances in the hypothalamic-pituitary-adrenal axis, seem to be of crucial importance that may account for the increased risk in mentally retarded subjects for the development of behavioural and psychiatric disorders within the affective, impulsive and anxiety spectrum .