Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first
human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ
preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft
function and surveillance of long-term complications have drastically increased recipient survival. However, there
are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key
role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding
side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization
of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart
failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant
morbidity and survival while preventing both rejection and complications of immunosuppression.
The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression
in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches
are provided. Cardiac allograft rejection classification and up-to-date management are summarized.
Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents
focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as
sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics
to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression
in heart transplantation are highlighted.