The management of patients on chronic oral anticoagulant therapy, namely Vitamin K antagonists such as warfarin, is often associated with difficult and challenging issues for the healthcare practitioner. Many of these issues, such as warfarin failure or resistance, the optimal warfarin initiation dose, the optimal target International Normalized Ratio in antiphospholipid syndrome, the optimal monitoring frequency and use of point-of-care monitoring, the management of oral anticoagulation during invasive procedures, and the management of over-anticoagulation, have not been evaluated in rigorously-designed clinical trials. The latest American College of Chest Physician recommendations concerning these issues are Grade 2C, the weakest recommendations available. It remains up to the experience and expertise of the individual practitioner along with whatever clinical evidence is available in a particular healthcare environment—especially one associated with an anticoagulant management service—to implement management strategies with respect to these issues in patients on oral anticoagulation.