Left ventricular assist devices (LVADs) have evolved into long-term use as destination therapy for those with severe end-stage heart failure due to other medical risks. Success with LVAD depends on adherence to a complicated mechanical regimen, and acceptance of a life that is far from normal. Patients with LVADs share characteristics with other end-stage cardiac failure patients and those waiting for or receiving heart transplants. Understanding the more thoroughly studied issues of psychiatric disorders, adherence, and behavioral correlates of success in heart failure and transplantation may identify feasible strategies for optimizing care of LVAD patients and suggest directions for future research. Depression and distress complicate post-transplant care. Psychiatric morbidity is associated with poor outcomes, including graft rejection, non-adherence, hospitalizations, infection, and death. With a high risk of embolic neurological events, patients’ ability for self-care may be compromised. Psychiatric symptoms are underdiagnosed and undertreated, which may impact overall survival and quality of life.