Platelets are lost from circulation by 2 mechanisms: senescence and random loss. Approximately 7.1 × 10 3 platelets/μL/d are postulated to be randomly used in maintaining vascular integrity. Thus, in clinically stable patients, major bleeding is unusual unless the platelet count is ≤5 × 10 3/μL. Risk factors for bleeding at higher platelet counts are disseminated intravascular coagulation with contributory clotting factor deficiencies, structural lesions with loss of vascular integrity, and refractoriness to platelet transfusions. Several large studies have documented the safety of lowering the prophylactic platelet transfusion trigger from the previously used 20 × 10 3/μL to 10 × 10 3/μL. A few studies have even suggested that a 5 × 10 3/μL trigger is acceptable. Based on these results, the next step of giving just therapeutic platelet transfusions is being evaluated. In a large retrospective study, the most significant predictor of bleeding was not the patient’s platelet count but a history of bleeding in the prior 5 days. These data suggest that attention should be focused on providing aggressive platelet therapy for active bleeding rather than transfusing platelets prophylactically. Therapeutic platelet transfusions have been documented to control bleeding, and mortality rates are not increased when comparing patients receiving therapeutic to that seen in patients receiving prophylactic platelet transfusions.