Liver transplantation is a life‐saving therapy for patients with end‐stage liver disease, acute liver failure, and liver tumors. Over the past 4 decades, improvements in surgical techniques, peritransplant intensive care, and immunosuppressive regimens have resulted in significant improvements in short‐term survival. Focus has now shifted to addressing long‐term complications and improving quality of life in liver recipients. These include adverse effects of immunosuppression; recurrence of the primary liver disease; and management of diabetes, hypertension, dyslipidemia, obesity, metabolic syndrome, cardiovascular disease, renal dysfunction, osteoporosis, and de novo malignancy. Issues such as posttransplant depression, employment, sexual function, fertility, and pregnancy must not be overlooked, as they have a direct impact on the liver recipient's quality of life. This review summarizes the latest data in long‐term outcome after liver transplantation. Mt Sinai J Med 79:169–189, 2012. © 2012 Mount Sinai School of Medicine