Due to familiarity, short half-life, ease of monitoring, and the availability of a reversal agent, heparin remains the anticoagulant of choice for cardiac operations requiring cardiopulmonary bypass (CPB). However, occasionally patients require CPB but should not receive heparin, most often because of acute or subacute heparin-induced thrombocytopenia (HIT). In these cases, if it is not feasible to wait for the disappearance of HIT antibodies, an alternative anticoagulant must be selected. A number of non-heparin anticoagulant options have been explored. However, current recommendations suggest the use of a direct thrombin inhibitor such as bivalirudin. This review describes the use of heparin alternatives for the conduct of CPB with a focus on the direct thrombin inhibitors. To view the article, click here.