Platelets are important actors of cardiovascular diseases (CVD). Current antiplatelet drugs that inhibit platelet aggregation have been shown to be effective in CVD treatment. However, the management of bleeding complications is still an issue in vascular diseases. While platelets can act individually, they interact with vascular cells and leukocytes at sites of vascular injury and inflammation. The main goal remains to better understand platelet mechanisms in thrombo-inflammatory diseases and provide new lines of safe treatments. Beyond their role in hemostasis and thrombosis, recent studies have reported the role of several aspects of platelet functions in CVD progression. In this review, we will provide a comprehensive overview of platelet mechanisms involved in several vascular diseases.