Recent studies have highlighted the complexity of platelet biology, revealing their diverse roles beyond hemostasis. Pathological platelet activation is now recognized as a key contributor to thrombosis and inflammation that are both central to cardiovascular disease (CVD). Emerging research emphasizes the significant impact of demographic factors – such as age, sex, race, and ethnicity – on CVD risk and responses to antiplatelet therapies. These population-based differences, shaped by genetic and non-genetic factors, highlight the need for reevaluation of antiplatelet strategies. We address current knowledge and emphasize the pressing need for further research into platelet biology and cardiovascular outcomes across diverse populations. In this review we advocate for tailored therapeutic approaches in CVD based on the recent demographic-focused findings.