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Platelets are essential mediators of the physiologic process of hemostasis and pathologic thrombosis. While platelets do not interact with vascular walls under normal conditions, vascular injury or inflammation result in a coordinated series of events including platelet adhesion, aggregation, and promotion of coagulation. In this review, we describe the primary mechanisms involved in these responses in various vascular beds of both macro- and microvessels, and outline key unresolved aspects of these important interactions. Table of Contents: Introduction / General Characteristics of Platelets / Platelet Adhesion to Vascular Walls / Platelet Aggregation / Platelet Recruitment and Blood Coagulation / Arterial, Venous, and Microvascular Hemostasis/Thrombosis / Summary