Thrombotic events including stroke, heart attack and deep venous thromboembolism are a leading cause of death and health complications. Hereditary and acquired risk factors lead to a hypercoagulable state, setting the stage for thrombosis. Anticoagulant therapy can reduce the risk for thrombosis. While traditional anticoagulants such as warfarin and heparin have been the mainstay of therapy, new anticoagulants such as dabigatran and rivaroxaban are now available. The clinical data leading to the use of these drugs will be reviewed. The role of laboratory testing to identify individuals at risk for thrombosis who may benefit from anticoagulant therapy and strategies for monitoring anticoagulants will be discussed.