Heart transplantation has, over the years, become the best treatment choice for patients with end-stage heart failure. The increase in longer waiting times among patients awaiting transplantation is due to scarcity of suitable donor organs. Major improvements in recipient and donor selection, perioperative management and postoperative follow-up such as immunosuppressive treatment and prevention of opportunistic infections have considerably enhanced the outcome of heart transplantation. This review will focus on the managements of these complex patients, as well as on some proposed changes to achieve better results.