Essential hypertension is a major risk factor for cardiovascular disease due to ischemic thrombotic events. The increased thrombotic tendency observed is partly mediated by enhanced platelet activation. Several putative mechanisms have been implicated in platelet activation and vascular damage in hypertension, among which increased oxidative stress and defective nitric oxide (NO) signaling are the most important. The increased oxidative burden in this context is an important mediator of abnormal platelet function, conferring a potent pro-aggregatory phenotype. In turn, platelets activated by oxidative stress are an additional source of reactive oxygen species, further contributing to circulating oxidative stress and reduced NO bioavailability. In addition, impairment of platelet NO signaling and lower levels of platelet-derived NO have been observed in essential hypertension, further contributing to endothelial dysfunction and thrombosis. In addition, overactivity of the renin-angiotensin and sympathetic nervous systems and increased shear stress have been also implicated in platelet activation and thrombosis. Platelet activation in turn fuels the release of several vasoactive molecules mediating thrombosis and vascular damage. More specifically, enhanced circulating vascular endothelial growth factor levels of platelet origin have been observed, suggesting a link between platelet-mediated angiogenesis and the prothrombotic state in hypertension. Finally, increased intraplatelet Ca2+ and platelet microvesicle release from activated platelets of hypertensive patients also confer a pro-aggregatory phenotype and contribute to vascular hyperreactivity.