The most important adverse effect of antiplatelet and anticoagulant therapy is the occurrence of bleeding. Gastroenterologists, cardiologists, and primary care physicians often find themselves balancing the benefits of antiplatelet and anticoagulant therapy with the risk of bleeding, namely gastrointestinal bleeding. While aspirin and warfarin have long been the mainstay of oral antiplatelet and anticoagulant therapy, respectively, recent discoveries of more precise targets for therapy have come to market in order to reduce the risk of cardiovascular events and overcome the wellknown limitations that plague warfarin therapy (e.g. narrow therapeutic index, variable individual metabolic response, and numerous food and drug interactions). Despite the fact that these novel agents may increase the risk of gastrointestinal bleeding , their ease of use makes them more attractive than conventional agents. This review will provide an overview of the pharmacology of available antiplatelet agents and anticoagulants, outline risks that clinicians should be cognizant of when considering prophylactic therapy in order to reduce the risk of gastrointestinal toxicity, and provide up to date data on reversal agents that are currently available as well as those that are in the pipeline.