According to the DSM-IV, all types of psychiatric disorders can be observed in mentally retarded subjects, with prevalence estimated to be three or four times higher than in the general population. Clinical features, longitudinal course and triggering factors are influenced by the characteristics of the intellectual disability. The aim of this paper is to discuss the specificity of the psychopharmacological therapy in mental retardation (sensitivity to specific psychotropic drugs, incidence of side effects, predictive criteria for evaluating risk factors, etc.) and to propose an update in the pharmacotherapy in the most important psychiatric disorders (mood disorders, psychotic disorders, behavioral disorders, anxiety disorders, attention deficit disorders with or without hyperactivity.