Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. The predominant symptoms of acute GVHD occur in the skin, liver, and intestine. Induction of acute GVHD can be divided into three phases: recipient conditioning, donor T cell activation, and effector cell-mediated GVHD. Chronic GVHD usually appears up to 100 days after HSCT and is characterized by symptoms similar to those observed for autoimmune disease. It is possible that chronic GVHD is the result of autoreactive T cells that escaped negative selection due to damage to the thymus from conditioning regimens, acute GVHD, and/or age related atrophy. Recent advances in the understanding of the basic mechanisms involved in GVHD pathophysiology have led to new strategies designed to block GVHD. This review focuses on recent developments in the treatment of GVHD, including insights gained from our own experimental studies.