Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care professional in order to test their international normalized ratio (INR). Newer anticoagulants, including dabigatran, rivaroxaban and apixaban, do not require frequent INR testing and have a quicker onset of action than warfarin, providing convenience for the patient. However, many health care professionals prefer warfarin because the INR may indicate its efficacy, its dosages can be easily changed and it is typically more affordable. Additionally, dabigatran may be chosen because it is the only one of these drugs that has a reversal agent, which can be utilized in the case of major bleeding or emergent surgery. There are many opportunities for pharmacists to impact patient outcomes in the anticoagulation therapy setting. From clinics to the community pharmacy setting, the pharmacist's role in patient counseling and education is crucial in reducing mortality. Additionally, drug development is a growing market as reversal agents are needed for many of these newer anticoagulation therapies.