Ischemic etiology accounts for two thirds of all strokes in which platelet activation and aggregation play a major role. A variety of antiplatelet therapies have been tested for primary, secondary and tertiary prevention, with specific patient subtypes benefiting more than others from a specific regimen. This review aims at synthetizing current evidence on pharmacology of antiplatelet agents approved for primary, secondary and tertiary stroke prevention and their application among possible subtypes that may benefit more their administration. Management of ischemic stroke has largely evolved over the past decades. A better understanding of stroke pathophysiology has allowed to identify patients who can benefit most from antiplatelet therapies, with varying degrees of benefit depending on whether these agents are being used for primary, secondary or tertiary prevention. Importantly, the antiplatelet treatment regimens currently available have expanded and no longer limited to aspirin but include other therapies such as P2Y12 and phosphodiesterase inhibitors, also used in combination, as well as precision medicine approaches using genetic testing aiming at optimizing the safety and efficacy in this population.