Coronary artery disease remains one of the most important causes of morbidity and mortality worldwide, with a disease burden that does not seem to have decreased significantly over time. Since their developments, oral drugs that are able to reduce the coagulation properties of blood (i.e., oral anticoagulants such as warfarin or dicoumarol) have been tested in thousands of patients with, or suspected with, coronary artery disease, however they have yielded disparate and conflicting results. The advent of oral antiplatelet agents has further put into a niche the apparent role of oral anticoagulant therapy in subjects with established coronary artery disease (i.e., in the setting of secondary prevention). However, the current and future role of oral anticoagulants in the secondary prevention of coronary artery disease remains very important, as testified to by the ongoing research by several major companies and investigators focusing on the development of novel oral anticoagulants. This review provides a succinct and updated appraisal of the long-term effects of chronic oral anticoagulation in the setting of coronary artery disease. © 2009 Future Medicine Ltd.