The efficacy of the serine protease inhibitor, aprotinin, and the lysine analogs, epsilon-aminocaproic acid and tranexamic acid, in reducing bleeding and transfusion in adults undergoing cardiac surgery is well established. Although children undergoing cardiac surgery are clearly at high risk for bleeding and transfusion, the risks and benefits of this therapy for the pediatric population are less well understood. There is a reasonable body of literature examining antifibrinolytic therapy in congenital heart surgery, but the large variability in patients studied, procedures, methods, and dosing schemes makes a quantitative analysis of this literature impractical. A qualitative review of this literature reveals significant support for the efficacy of all three drugs for decreasing bleeding and transfusion in congenital heart surgery, likely with more benefit in certain populations. Limited data suggest that there is no difference in efficacy among the three drugs, although aprotinin may have unique antiinflammatory effects that are of benefit in pediatric patients. There is not enough evidence to draw any conclusions about the safety of these drugs in children, although it appears that the risk of anaphylaxis with aprotinin in children may be less than in adults. Dosing schemes used for these drugs have been variable and not always based on sound pharmacologic principles, despite available pharmacokinetic and pharmacodynamic data. Further research should be directed toward establishing safety, evaluating the relative efficacy of the two classes of drugs, proving benefit in specific patient groups, and better defining effective dosing schemes.