The advancing science of transplantation has led to more transplants and longer survival. As a result, primary care physicians are more involved in the care of transplant recipients. Immunosuppressive therapy has significantly decreased rates of transplant rejection but accounts for more than 50% of transplant-related deaths, often due to infections and other risks related to long-term use. Cardiovascular disease is the leading cause of non-transplant-related mortality. Aggressive risk factor management is recommended for transplant recipients, including a blood pressure goal of less than 130/80 mm Hg and statin therapy in kidney, liver, and heart recipients. Fertility typically increases posttransplant, and female transplant recipients should avoid pregnancy for one year after surgery. The best contraceptive choice is usually an intrauterine device. Because of the increased risk of infection, patients should be tested for graft dysfunction or infection if suspicion arises. Testing should be coordinated with the transplant center. Malignancies are a common cause of death in transplant recipients, requiring careful attention to screening recommendations and informed discussions with patients. Family physicians should maintain an ongoing relationship with the transplant team to discuss medication changes and the risk of infection or graft rejection.