The chapter describes the history, mechanisms and phases of drug treatment of antipsychotics including at-risk mental states (ARMS), first-episode psychosis (FEP), maintenance, treatment-resistant schizophrenia (TRS) and ultra-resistant psychosis. Specific treatments of schizoaffective disorder, catatonia and affective comorbidities of psychosis target negative symptoms and cognition. Rapid tranquilisation is described: general principles, de-escalation, routes of administration and medication selection. Management of organic psychotic disorders is discussed: general principles and specific conditions, epilepsy, Huntington’s, stroke, drug-induced, autoimmune encephalitis, inflammatory, CNS infections, thyroid disorders and traumatic brain injury. Side effects are elaborated: somnolence and sedation; hyperprolactinaemia and sexual dysfunction; motor, cardiac, metabolic and anticholinergic side effects; and also diabetes and impaired glucose tolerance and clozapine-specific side effects. Finally, potential drug interactions are explored.