Despite the development of new anticoagulants, unfractionated heparin (UFH) continues to be a primary choice for intravenous anticoagulant therapy because of its titratability, short half-life, ability to use in patients with renal failure, and acute reversibility. UFH continues to be the mainstay of parenteral anticoagulation especially in critically ill patients and to maintain anticoagulation during mechanical cardiopulmonary support. As with all intravenous anticoagulants, monitoring is required for its use. In critically ill patients, UFH can be monitored by multiple tests that include the activated partial thromboplastin time (aPTT), heparin activity measured by antifactor Xa (anti-Xa), or activated clotting time (ACT). Although the aPTT and the ACT are frequently used for monitoring, there are multiple limitations. Anti-Xa heparin monitoring represents an important alternative, and I routinely used anti-Xa monitoring as our standard of measurement in my previous institution. However, aPTT is the standard for monitoring in my current institution. Despite this, I frequently use anti-Xa monitoring as an important guide to therapy especially in critically ill, complex patients especially during ECMO and mechanical cardiopulmonary support. Anti-Xa monitoring is a more direct measure of UFH activity than the aPTT, demonstrates less variability and is most helpful when conflicting values occur during aPTT monitoring. In this presentation, I will review UFH monitoring focusing on the use of the anti-Xa for critically ill and general patient management.