Uremic patients develop an acquired platelet dysfunction that results in bleeding complications. The pathogenesis of this hemostatic dysfunction is multifactorial and includes effects of circulating toxins, alterations of the vessel wall, anemia, and other factors, complicated by unwanted effects of hemodialysis procedures. This review seeks to place in perspective the evolution of knowledge on uremic platelet dysfunction. It examines how investigations of the altered hemostasis in these patients have led to a better understanding of the mechanisms involved and how these advances have contributed to the development of effective therapeutic strategies. It also comments upon the fact that elevated rates of thrombotic complications are apparently emerging as the bleeding tendency is better controlled. Emphasized is the delicate balance of hemostasis in the uremic condition, in which deficient hemostasis paradoxically coexists with accelerated atherosclerosis and an enhanced risk of thrombosis.