Chronic graft versus host disease (GVHD) remains today one of the most vexing late complications of allogeneic stem cell transplantation. Occurring a minimum of 100 days following stem cell transplantation, approximately 50% of patients will experience some degree of chronic GVHD. Host-reactive lymphocytes of donor origin are the cells responsible for the "alloimmune" attack. The increased use of hematopoietic stem cells collected from the peripheral blood instead of bone marrow and the increasing age of stem cell transplant recipients has led to a higher incidence of chronic GVHD. Chronic GVHD most commonly affects the skin, liver, eyes or the mouth, however multiple other sites may also be affected. Chronic GVHD and the medications used to treat it result in a profoundly immunocompromised state. Death due to severe chronic GVHD is usually a consequence of infectious complications. Standard treatment for severe chronic GVHD is a combination of cyclosporine and prednisone. An alternating day regimen of these two agents prolongs survival and reduces drug-related adverse events. Topical therapy to affected areas is preferred for patients with mild disease. The 10-year survival of patients with mild chronic GVHD is approximately 80%, but is less than 5% for patients affected by severe chronic GVHD.