Acute graft-versus-host disease (aGVHD) is the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation. It represents the immune reaction of immunocompetent T cells of a mismatched donor to recipient cells which it recognizes as foreign. The mechanism of occurrence takes place in three phases. The use of radiation and intensive chemotherapy to prepare patients for transplantation results in injuries to the patient's tissues due to the secretion of inflammatory cytokines (phase I). These inflammatory cytokines and antigen-presenting cells activate aGvHD by T donor lymphocytes (phase II) and stimulate macrophages by cytokine secretion and endotoxins. Macrophages with cellular inflammatory effectors secrete cytokines and lead to local tissue injury (phase III). It classically appears within hundred days after transplantation. It can affect one or more organs: skin, liver, and gastrointestinal tract. Typical skin changes are maculopapular rash, generalized erythema and in the most severe cases, epidermolysis with bumps and desquamation as possible. Changes in the liver manifest as hyperbilirubinemia with jaundice and an increase of alkaline phosphatase and serum cholesterol, while changes in the gastrointestinal tract manifest as nausea, diarrhea, and abdominal pain. The diagnosis is based on the clinical signs and histological findings of a biopsy of the skin, rectum and rarely liver. In prophylactic therapy calcineurin inhibitors are most usually used (cyclosporine or tacrolimus), alone or in combination with other immunosuppressive drugs (most usually methotrexate in patients after myeloablative preparation) and mycophenolate mofetil in patients after nonmyeloablative preparation. Therapy depends on symptoms, organ involvement and prophylaxis – the first stage does not require systemic treatment, while the first choice of therapy for other stages are systemic corticosteroids. If the first-line treatment fails, the second-line therapy is ruxolitinib, a new drug with high efficacy in the treatment of acute GvHD. Other choice of drugs and therapeutic procedures in treatment are antithymocyte globulin, mycophenolate mofetil, monoclonal antibodies, pentostatin, sirolimus, mesenchymal stem cells and extracorporeal photopheresis.