The purpose of this article is to give an insight into current trends of immunosuppression in heart transplantation. Presently available classes of drugs: steroids, antimetabolites, polyclonal and monoclonal antibodies, calcineurin inhibitors, proliferation signal inhibitors have been described closely. These drugs are in use either in a prophylactic manner or as the part of the maintenance immunosuppressive regimen. Induction therapy provides immune suppression as key point to induce graft tolerance. The backbone of immunosuppression in organ transplant recipient: cyclosporine A and tacrolimus have been widely used as maintenance therapy in combination with adjunctive immunosuppressant. We also mentioned the immunosuppressive agents in development: lymphocyte modulation therapy, tolerance induction drugs, gene therapy possibilities and xenotransplantation as option to overcome the organ shortage. After heart transplantation immunosuppressive medications are used to reduce the risk of donor`s organ rejection. The focus is to prevent graft rejection, since host immune system is programmed to attack foreign antigens which could cause injuries and lifethreatening conditions. The possibility of rejection is everlasting, which inevitably demands the use of immunosuppressive drugs and raise the risk of unwanted side effects. Post-operative complications include hyper acute, acute or chronic rejection, as well as post-transplant lymphoprolipherative disorders, and permanent susceptibility to various infections. Unfortunately, some recipients developed the renal failure or malignant diseases due to the aggressive immunosuppression. Immunosuppressant agents differ not only in mechanism of action but also in undesirable side effects. This offers an opportunity to combine drugs with synergistic actions and chance to successfully tailor anti-rejection therapy after heart transplantation.