The ability of high concentrations of recombinant factor VIIa (rFVIIa) to improve thrombin generation in in vitro and ex vivo models of thrombocytopenia, and to improve bleeding time in thrombocytopenic animal models supports a potential role for rFVIIa in the management of thrombocytopenic bleeding. Anecdotal reports suggest that rFVIIa is effective in the prevention and treatment of bleeding episodes in surgical procedures in a limited number of patients with severe thrombocytopenia. There is a need for clinical trials to determine whether rFVIIa is efficacious and safe in severe thrombocytopenic bleeding, either by itself or in combination with other hemostatic agents such as platelet transfusion. Pending the availability of such data, rFVIIa may be considered in severe thrombocytopenic bleeding that is unresponsive to human leukocyte antigen-compatible platelet transfusions and other standard treatments. If rFVIIa is used, unresolved issues include optional dosage, dosing interval, and whether rFVIIa is best used alone or in conjunction with platelet transfusion.