In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.