ST-segment elevation myocardial infarction (STEMI) is a serious manifestation of atherothrombosis. Platelets play an important role in the pathogenesis of atherothrombosis, and the use of antiplatelet agents is associated with substantial improvements in clinical outcome. Current guidelines for the management of patients with STEMI stress the importance of using antiplatelet agents as an integral part of acute and long-term therapy. However, these and other recommended therapies are frequently underutilized. In-hospital quality improvement initiatives have been shown to substantially improve adherence to guideline-recommended therapies at the time of discharge. This review discusses the role of platelets in atherothrombosis and describes the medical management of patients with STEMI, highlighting current guideline recommendations, adherence in clinical practice, and the impact of quality improvement programs in maintaining the continuum of care into the ambulatory setting.