Endometrial carcinoma is the most common gynecologic cancer in developed nations, and the annual incidence is projected to increase, secondary to the high prevalence of obesity, a strong endometrial carcinoma risk factor. Although endometrial carcinomas are etiologically, biologically, and clinically diverse, hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid carcinoma, the numerically predominant subtype. The centrality of hormonal and metabolic disturbances in the pathogenesis of endometrial carcinoma, combined with its slow development from well-characterized precursors in most cases, offers a substantial opportunity to reduce endometrial carcinoma mortality through early detection, lifestyle modification, and chemoprevention. In this chapter, we review the epidemiology of endometrial carcinoma, emphasizing theories that link risk factors for these tumors to hormonal and metabolic mechanisms. Future translational research opportunities related to prevention are discussed.