Immunosuppression following cardiac transplantation can be divided into early rejection prophylaxis, chronic maintenance, and the treatment of established episodes of allograft rejection. Early rejection prophylaxis is the immunosuppressive protocol administered in the first few weeks following transplantation and consists of cyclosporine, azathioprine, and corticosteroids with or without the addition of specific anti-T cell agents such as antithymocyte globulins, antilymphoblast globulins, or the murine monoclonal anti-CD3 antibody (OKT3). Most programs now use triple therapy (cyclosporine, azathioprine, and prednisone) as chronic maintenance immunosuppression, although the feasibility of corticosteroid-free maintenance has been demonstrated. The treatment of acute allograft rejection involves optimization of cyclosporine and azathioprine doses along with the augmentation in corticosteroids and with or without the addition of a specific anti-T cell agent, depending on the histological grade hemodynamic consequences of the rejection episode. Further individualization of immunosuppressive therapy is likely to occur in the future.