Heart-lung transplantation was, for many years, conceptualized as a possible treatment for patients with combined end-stage cardiac and pulmonary disease. As experience grew with heart transplantation, particularly in the 1970s, the difficulties of performing the orthotopic operation in patients with fixed pulmonary hypertension became apparent. This further impetus for combined heart-lung transplantation led to successful animal experiments in the late 1970s, and the first successful heart-lung transplant operation was performed in 1981. There has been significant evolution in the operative technique for the recipient operation, with emphasis on preservation of the phrenic, vagal, and recurrent laryngeal nerves and on meticulous hemostasis, with particular attention to the bronchial vessels of the posterior mediastinum. Donor procurement is of critical importance to the success of the operation, and criteria for donor selection have been well established. Lung preservation remained, for many years, a significant limitation, but current techniques involving the use of prostaglandin E1 have led to safe distant procurement with ischemic times up to 6 hours. The heart-lung transplant operation remains an effective modality for the treatment of patients with congenital heart disease, primary pulmonary hypertension, chronic obstructive pulmonary disease, and cystic fibrosis.