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Acute coronary syndromes (ACSs) account for a large proportion of disease burden in the United States and worldwide, and our understanding of ACS management continues to evolve. In this review we take a practical approach to evaluating and treating a patient with ACS, focusing on the optimal timing and methods of coronary reperfusion. Beginning with initial assessment and risk stratification, a provider managing the patient with ACS must be able to expeditiously decide on and implement the correct guideline-directed pathway to optimize outcomes. With an ever-growing body and weight of knowledge in this field, the clinician is tasked with several challenges. First, there are a variety of pathways of care to be considered; second, adjunctive medical therapies are expanding; and third, when coupled with the multiple combinations of adjunctive supportive therapies for revascularization, the variety of potential therapeutic options can be overwhelming and confusing. Herein, we carefully review all the relevant guidelines and the contributing literature, taking a 4-step approach: (1) review the importance of risk stratification before engaging in a particular strategy of care, (2) define the reperfusion strategies available, (3) review the specific agents (antiplatelet and anticoagulant) that support reperfusion strategies, and (4) apply the strategies of care in the context of the clinical presentation.