Psychosis arises from a complex interaction between genetic and environmental factors. Knowledge about biological aspects is paramount for professionals who provide mental health services to people with intellectual disabilities who develop psychosis. This chapter includes core biological aspects: aetiology, comorbid intellectual disabilities and psychosis, and additional physical and mental health conditions, psychopharmacology, and adverse effects from antipsychotic medication. A case study will illustrate how a combination of conventional diagnostic assessment based on symptoms and impaired functioning along with newer insights into the biological aspects of psychosis can facilitate diagnostic work and effective treatment.