Patients undergoing hemodialysis (HD) are at high risk for both atherothrombosis and hemorrhage. Compared to healthy individuals, these patients show significant alterations in platelet dynamics, potentially contributing to cardiovascular complications and bleeding. This review presents a hypothesis-generating model to elucidate the mechanisms of platelet turnover, reactivity, and premature aging in HD patients. It also examines the roles of pulmonary thrombopoiesis, inflammation, and oxidative stress in platelet dysfunction. Furthermore, the review highlights the importance of platelet heterogeneity and proposes a strategy for developing personalized antiplatelet therapies for HD patients. Future research directions, such as single-cell analyses, are recommended to enhance understanding of platelet dynamics in HD and improve patient care.