Apart from morbidity related to the allograft, post-transplant complications are often related to the long-term use of immunosuppressive therapy. In addition, post-transplant morbidity may also be related to the medical conditions that lead to the need for heart transplantation in the first place. In this chapter, we review the incidence, pathophysiology and management approaches to key post-transplant complications—hypertension, renal dysfunction, diabetes mellitus, malignancy, arrhythmias, osteoporosis and sexual dysfunction.