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Platelets, the cellular fragments of their precursor megakaryocytes, play an important role in hemostasis and other pathophysiological circumstances including atherothrombosis and atherosclerosis. Activated platelet not only can aggregate with each other to form the thrombi, but also can interact with leukocytes in the circulation to form the platelet-leukocyte aggregates (PLAs). Increased number of PLAs has been reported in patients with atherosclerosis or atherothrombosis, and animal models using different knock-out mice have unraveled the molecular mechanisms underlying the platelet leukocyte interaction. This review describes the platelet leukocyte interaction in atherosclerosis and atherothrombosis by integrating our knowledge of basic mechanisms of platelet leukocyte interaction from animal studies with the clinical studies illustrating the platelet leukocyte interaction in patients with atherosclerosis.