The fields of heart and combined heart-lung transplantation continue to evolve, allowing treatment of more individuals with end-stage heart and lung disease. The postoperative course and rehabilitation phase may be arduous, emphasizing the importance of selecting candidates who meet specific medical and psychosocial criteria. Life-long immunosuppression and meticulous long-term medical surveillance are mandatory practices to promote the health of the recipient. The major complications that contribute to morbidity and mortality, especially during the first post-transplant year, are infection and rejection. Graft atherosclerosis, obliterative bronchiolitis, and malignancy are long-term complications that may limit survival. In spite of the emotional and physical challenges related to potentially life-threatening complications and other disturbances in daily living, the quality of life for most recipients has markedly improved.