The prevalence of psychiatric disorders is increased in children and adults with intellectual disability. Brain damage or dysfunction interact with social and family factors to increase susceptibility to mental illness. Psychiatric disorders in the context of genetic syndromes are commonly overlooked, and there is substantial underdiagnosis of mental disorders because of the atypical and non-specific clinical presentations, and the frequent assumption that psychiatric symptoms are an inherent part of the underlying intellectual disability. There is a strong need for evidence-based practice in the prescribing and monitoring of drugs in this population, especially since many of the drugs are unlicensed for use in children. There is an urgent need to understand and establish the pharmacokinetics, pharmacodynamics, and side-effect profiles of psychotropic medication in this population. Positive trends in pharmacotherapy include the use of atypical antipsychotics instead of the classic antipsychotics, serotonin-specific reuptake inhibitors (SSRIs) rather than tricyclic antidepressants, and newer antiepileptic drugs. Another welcome trend is the use of SSRIs instead of antipsychotics in the long-term management of challenging behaviour in this population.