Definite evidence has confirmed that platelets play a major role in thrombus formation and embolization, especially in the arterial system. In addition, increasing evidence has now shown that platelet deposition and thrombus formation can contribute to the growth and progression of atherosclerotic plaques. For these reasons, considerable attention has been focused recently on the question of whether drugs that inhibit certain platelet functions can prevent or modify the course of arterial thromboembolic disease and atherosclerotic disease in humans. In this first part, we review the current understanding of the role of platelets in thrombus formation, especially in the arterial system. This section comprises (1) the phases of arterial thrombus formation and its ultrastructural and biochemical basis, (2) the clinicopathologic presentation and fate of the arterial thrombus, and (3) the role of laboratory tests in its detection.