Fibrinolysis is an integral component of hemostasis that acts to regulate fibrin formation. Its actions are counterbalanced by the coagulation process, maintaining against excess clot formation or hemorrhage. Excessive release of plasmin through surgery or other means can result in a pathophysiological state characterized by bleeding, inflammation, and coagulopathy. Measurement of this fibrinolytic activity is often done in the clinical setting using viscoelastic testing; however, there is no gold standard. The antifibrinolytics tranexamic acid, epsilon-aminocaproic acid, and aprotinin act to reduce bleeding and transfusion requirements in the perioperative setting. Despite widespread concerns for thromboembolic complications, data has shown their relative safety. Tranexamic acid has been the most widely studied and utilized agent and is well tolerated with minimal side effects. The concern for seizure activity, particularly associated with cardiac surgery, has been diminished with appropriate dosing of tranexamic acid. The popularity of tranexamic acid in trauma is based on the CRASH-2 study, but the controversy surrounding fibrinolytic shutdown has limited its use in many centers. Orthopedics, liver surgery and transplantation, obstetrics, neurosurgery, and pediatric surgery have all extensively studied and implemented tranexamic acid to reduce blood loss and transfusion requirements.