Left ventricular assist devices (LVADs) driven by external sources and capable of sustaining life over weeks to months as a bridge to heart transplantation have been implanted in over 300 patients in the United States. Because of the limited availability of organs for transplantation, the remarkable degree to which LVADs reverse end-organ dysfunction, and patient acceptance, proposals for home LVAD treatment and for use of the LVAD as a permanent treatment for heart failure are being considered. LVAD therapy is associated with characteristic psychiatric and psychosocial problems, however, which must be addressed to optimize results. Among the first 30 LVAD patients treated at our center, psychiatric interventions were frequently required for family stress, major depression, organic mental syndromes, and serious adjustment disorders. Psychiatric problems most often occurred in patients with ongoing medical complications following LVAD implantation, and often significantly impaired rehabilitation. Both depression and organic mental syndromes were frequently associated with preexisting cerebrovascular disease, which was sometimes occult, and with strokes complicating LVAD therapy. Aggressive treatment of depression played a major role in improving functional status. LVADs may decompress heart transplant waiting lists and make it possible to optimize patients' physiological and functional status before transplantation. With increased LVAD use, however, neuropsychiatric factors can be expected to play a large role in determining quality of life and outcome both before and after heart transplantation.