Platelets are critically involved in the pathophysiology of acute coronary syndromes (ACS). At the site of coronary plaque rupture, platelets adhere to exposed collagen in the bloodstream, accumulate, and trigger thrombosis, thereby restricting coronary blood flow and causing myocardial ischemia. Platelet adhesion, mediated by the interaction of vWF, platelet GPIb-IX-V, and collagen receptors α2β1 and GPVI, then triggers platelet hyperreactivity. Beyond conventional activation cascades, intracellular signaling pathways linked to thromboinflammation promote platelet aggregation and occlusive thrombus formation. Antiplatelet therapy targeting specific platelet receptors remains the cornerstone in the treatment and secondary prevention of ACS. Over the past decade, intensified antiplatelet strategies have significantly reduced thrombo-ischemic events, though this comes with an increased bleeding risk. Emerging antiplatelet and anticoagulant treatment regimens, including downstream mediators, have shown promising results that may offer safer options in the future for high-risk cardiovascular patients. This chapter explores the role of platelets in ACS, with a special focus on these intriguing but still underexplored mechanisms.