Hemostatic challenges occur throughout the period of stem cell transplantation (SCT). Endothelial cells injury due to chemotherapy, growth factors, intravenous catheter, and graft-versus-host disease and profound thrombocytopenia are the major components involved in the hemostatic complications. Diffuse alveolar hemorrhage and hemorrhagic cystitis are severe complications in SCT recipients with high morbidity and mortality rate and no effective treatment. Common thrombotic manifestations include Veno-occlusive disease (VOD) and central venous lines thrombosis. More intensive conditioning regimens and mismatch donors increase the risk of hemostatic complications. Management of hemostatic and thrombotic complications is discussed including current data on the role of recombinant factor VIIa for severe hemorrhage and defibrotide for VOD.