The transplant patient's therapeutic regimen consists of a lifelong drug therapy, including immunosuppressive drugs, prophylactic antimicrobials and often medications for the treatment of hypertension, diabetes mellitus and other comorbid diseases. Regular clinic appointments are required to monitor for signs and symptoms of immunological injury, recurrent disease and adverse drug effects. Patients are instructed to avoid risk factors for cardiovascular disease and cancer (e.g. diet, exercise, sun protection and not smoking). Noncompliance with all aspects of this regimen is substantial. Medication noncompliance leads to an increased incidence of acute rejection, chronic rejection and graft loss. Undoubtedly, many practitioners fail to appreciate the extent of noncompliance as the signs are often subtle and most patients are unwilling to disclose deliberate or widespread disregard for medication use. Newer immunosuppressive agents, particularly once-daily medications and long-acting antibody preparations offer convenience and monitoring that may improve compliance. This review focuses on the prevalence, correlates and consequences of medication nonadherence after organ transplantation. Current recommendations to enhance adherence are discussed.