Cardiac surgery involving cardiopulmonary bypass imposes a significant pathophysiologic burden on patients. Pediatric patients are especially predisposed to the adverse effects of surgery and bypass on the coagulation system, with resultant bleeding, transfusion, and poor outcomes. These risks accrue to pediatric patients in inverse proportion to their weight and are attributable to hematologic immaturity, coagulation defects associated with congenital heart disease, bypass equipment, and the nature of congenital heart surgery. Standard anticoagulation does not completely inhibit thrombin generation, and continuous consumption of coagulation factor continues throughout bypass. Conventional measurements of anticoagulation during bypass poorly reflect this incomplete anticoagulation, and alternate methods may improve anticoagulant therapy. Emerging therapies for blocking the effects of bypass on the coagulation system hold promise for decreasing bleeding and related complications, and improving outcomes in congenital heart surgery.