Despite improvements in the treatment of acute coronary syndromes (ACS), cardiovascular disease remains the leading cause of death in the United States. Antiplatelet agents, such as aspirin and clopidogrel, play an important role in the treatment of patients with ACS, particularly those at high risk for whom treatment may yield the greatest benefits. The main challenge in preventing and managing ACS is to tailor treatment for each patient by taking into consideration patient characteristics, comorbidities, underlying short- and long-term risk factors, ischemic and bleeding risks, and expected individual responses to different medications. Several new alternatives providing more rapid and consistent platelet inhibition than aspirin and clopidogrel have been introduced for routine treatment of patients with ACS. These new treatments seem to provide additional benefits without a significant increase in the risk of bleeding, if used for the appropriate patients. In this article, we review the new antiplatelet agents being developed as well as their pharmacological characteristics, potential clinical indications, and key interactions with other antithrombotic drugs.