Transplantation provides life-saving therapy to critically ill patients with end-stage organ failure. We found that the specialized knowledge of mental health clinicians and physicians, committed to the evaluation and management of transplant recipients, is essential for the optimal care of these patients who require a life-long regimen of immunosuppressive medication and dependency on the transplant team. Critical issues requiring psychiatric input are frequently encountered in the following areas (1) patient selection and informed consent; (2) recognition and pretransplant treatment of psychiatric disorders; (3) substance or alcohol abuse; (4) compliance with medical regimens; (5) posttransplant psychosis; and (6) immunosuppressive/psychiatric drug-drug interactions. This review focuses on the priorities in psychological and psychiatric care of these unique patients.