The physiological imbalances associated with organ insufficiency and the complexity of organ transplant surgery and postoperative care puts patients at risk for psychiatric disorders. The brain is susceptible to a variety of insults as a result of these complex processes, including those secondary to medications and infections. We review literature relevant to organ transplant patients and also include empirical knowledge based on clinical practice. We first describe the physiologic and psychiatric issues for each major organ that is commonly transplanted, including liver, kidney, heart, bone marrow, and pancreas, as well as multiple organ transplantation. We then discuss the pharmacologic treatment and neuropsychiatric side effects of rejection with various immunosuppressants, including cyclosporine, azathioprine, OKT3, FK506, and corticosteroids. Certain bacterial, fungal, viral, and protozoal infections occur more frequently in the transplant population; their relationship to neuropsychiatric dysfunction is discussed. We then present details of psychopharmacotherapy of delirium, other organic mental disorders, depression, mania, anxiety, and insomnia, with attention to drug interactions and differential diagnosis. Particularly cautious monitoring of medication doses and serum levels is recommended in these patients.