No wholly satisfactory drug or system has yet been devised for preventing thrombosis in extracorporeal blood circuits needed for renal replacement treatments. Heparin is still regarded by some as a standard approach, but advances in many areas of intensive care unit (ICU) medicine have created the potential for saving the lives of many patients in whom heparin anticoagulation is no longer appropriate. Several nonheparin methods are now readily performed, and the great risk of bleeding that is imposed by the use of heparin demands that citrate or other nonheparin methods be made available in the ICUs of all major medical centers that deal with trauma or major surgical procedures. Details of the practicalities, difficulties, and advantages are compared for low-dose heparin, regional heparin, low-molecular-weight heparin, no-anticoagulant systems, citrate, and other anticoagulants for both intermittent and continuous modalities. The clinical features and complications in individual patients that impact on the selection of the best method of management are reviewed.