The purpose of this review is to describe the hemostatic changes induced by extracorporeal membrane oxygenation (ECMO), the need to balance the risks of bleeding and clotting with anticoagulation and hemostatic transfusions, and the inherent risks to these interventions. Both bleeding and clotting are frequent complications of ECMO. To prevent clotting events, virtually, all children are anticoagulated. However, the optimal anticoagulation strategy is unknown. A recent systematic review of observational studies showed that anti-Xa-guided strategies were associated with a two-fold decrease in bleeding and no increase in clotting complications. These results need to be tested in randomized controlled trials. To avoid bleeding events, platelet transfusions are frequently prescribed to children on ECMO. However, platelet transfusions have recently been shown to be independently associated with increased bleeding and clotting. Therefore, the optimal platelet transfusion strategy must be evaluated appropriately. Most patients on ECMO will develop either a hemorrhagic or thrombotic complication. Balancing these risks involves careful titration of anticoagulation to prevent clotting and hemostatic transfusions to prevent bleeding. As the current level of evidence is low, prospective randomized trials are needed.