Combined heart-lung transplantation (HLTx) is a surgical treatment for highly specific patients with advanced cardiopulmonary failure. Although the rates of patients undergoing HLTx have decreased over time, a few select centers continue to offer the procedure. Current indications include Eisenmenger syndrome with an uncorrected intracardiac defect, uncorrectable congenital heart disease with atresia or diffuse severe hypoplasia of the pulmonary arteries, and coexistent severe cardiopulmonary disease with advanced heart or lung failure. This chapter will outline aspects of thoracic transplantation that are specific to HLTx.