Graft-versus-host disease not associated with stem cell transplantation is a rare event, but might be underdiagnosed. It occurs mainly as transfusion-associated graft-versus-host disease in a susceptible recipient between day 2 and 30 after transfusion of cellular blood components, which also contain lymphocytes. These transfused lymphocytes are the causative agents. Their major target is the bone marrow, resulting in bone marrow failure leading to pancytopenia and consecutive death. The fatality rate is high (approximately 90 %). Patients at risks are those with congenital or acquired immunodeficiencies. However, immunocompetent patients may also be affected. This is the case when human leukocyte antigen (HLA)-homozygous donors share one haplotype with the recipient or when HLA-matched components are selected. The diagnosis is mainly a clinical one, supported by laboratory findings in biopsies from the skin and bowel. The detection of chimerism by HLA typing or short tandem repeat polymorphism can confirm the diagnosis. So far, no reasonable treatment exists, so prevention is still the only effective measure. Gamma irradiation has been used for years with great success. However, also pathogen inactivation, although developed to minimize the infectious risk of blood components, has shown, as a beneficial by-product, to reduce the number of lymphocytes. Other graft-versus-host diseases not associated with stem cell transplantation are those occurring after solid organ transplantation, e.g., after liver or small bowel transplantation, which have a similar pathophysiology and bad prognosis.