Extracorporeal membrane oxygenation (ECMO) is a method of life support to maintain cardiopulmonary function. Its use as a medical application has increased since its inception to treat multiple conditions including acute respiratory distress syndrome, myocardial ischemia, cardiomyopathy, and septic shock. While complications including neurological and renal injury occur in patients on ECMO, bleeding and coagulopathy are most common. ECMO is associated with an inflammatory response promoting a hypercoagulable state, requiring anticoagulation to avoid thromboembolism originating in the nonendothelial surfaced circuit. However, excessive anticoagulation may result in bleeding complications including intracerebral hemorrhage. Monitoring anticoagulation for ECMO has its origins in cardiopulmonary bypass for cardiac surgery; however, there is no ideal level of anticoagulation, no standardized method to monitor anticoagulation, nor are all centers standardized on what is used for anticoagulation. Multiple blood products are used in an effort to decrease bleeding in the setting of anticoagulation, often in the setting of recent surgery, and this leads to significant increases in cost for patients on ECMO and transfusion-related complications. In this review article, we discuss the evolution of the various modalities of ECMO, indications, contraindications, and complications. Furthermore, we review the different strategies for anticoagulation and treatment of coagulopathy while on ECMO. Finally, we discuss the cost of ECMO and associated blood product transfusion.