Cardiac transplantation is the treatment of choice for refractory heart failure. An immunosuppressive therapy must be given in the perioperative course to avoid graft rejection. In this article, we review the main classes of immunosuppressive agents (calcineurin inhibitors, anti-metabolities, corticoïds) and their side effects. The general preventive measures and the different kinds of rejection (hyperacute, acute vascular, acute cellular and chronical) are discussed. The current bacterial, protozoarian, mycotic and viral infections are described. We finish with the risk of cancer, mainly skin tumours and non-Hodgkinian lymphomas.