Acute graft-versus-host disease is a complication that affects 30-60% of patients undergoing allogeneic stem-cell transplantation. The standard for prophylaxis for graft-versus-host disease has historically been the combination of cyclosporine and methotrexate. Recently, tacrolimus has been used more frequently and current studies are exploring the potential of mycophenolate mofetil. There is little published experience with the use of sirolimus in prophylaxis or treatment but studies are ongoing. There have been significant advances recently in the treatment of steroid-refractory acute graft-versus-host disease. Historically, antithymocyte globulin was used when patients did not respond to the steroid treatment. New monoclonal antibodies such as daclizumab, and tumor necrosis factor alpha inhibitors such as infliximab are producing more promising results. Chronic graft-versus-host disease continues to be a major complication of stem-cell transplantation, affecting 35-50% of patients. Finding effective treatments for chronic graft-versus-host disease other than steroids continues to be a challenge.