Optimal outcome after heart, lung, and heart-lung transplantation can only be obtained if patients are supported in adhering to a lifelong therapeutic regimen. The transplant patient's therapeutic regimen consists of a lifelong medication regimen, including immunosuppressive drugs; monitoring for signs and symptoms related to complications; avoidance of risk factors for cardiovascular disease and cancer (ie, diet and exercise prescriptions, nonsmoking); avoidance of abuse/dependence of alcohol or illegal drugs, as well as attending regular clinical checkups. Nonadherence to all aspects of this regimen is substantial. Nonadherence has been related to negative clinical outcome in view of acute rejections, graft vasculopathy, higher costs, and mortality. This review focuses on the prevalence, correlates, and consequences of nonadherence to the therapeutic regimen in heart, lung, and heart-lung transplantation. The current state of the-art on adherence-enhancing interventions is reported. Priorities for future research are outlined.