THE SKIN is a major target organ for both acute and chronic graft versus host disease (GVHD) after stem cell transplantation (SCT). Although SCT is a life-saving measure and the treatment of choice for many patients with various hematologic malignancies, a high incidence of complications and a transplantation-associated mortality of approximately 30% are to be expected. GVHD is the major cause of morbidity and mortality at any time following SCT. The acute form occurs during the first 100 days after transplantation in up to 50% of graft recipients, whereas chronic GVHD develops in approximately 30%–50%, usually within 100–500 days following allogenic SCT. Target organs in GVHD can be all of those with lymphoid cells as well as epithelial structures, especially the skin, liver, gastrointestinal (GI) tract, lung, eyes, and neuromuscular system. Early diagnosis of GVHD can be difficult because drug reactions, viral infections, and cutaneous reactions to radiation therapy may have similar clinical and histological similarities. Histological findings of GVHD correlate poorly with clinical severity of the disease and have a limited role in predicting disease stage and progression. The skin manifestations, histopathologic features, prophylaxis, and therapy of acute and chronic GVHD are presented in this chapter.