Extra-fascial total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection is the initial treatment for endometrial cancer. Unresolved scientific controversy exists regarding the selection of patients who may benefit from lymphadenectomy, the magnitude of such benefit, and the role of adjuvant therapy. External pelvic irradiation has been shown to reduce loco-regional recurrences without improving survival. Meta-analyses of randomized trials indicate that external pelvic irradiation offers a significant benefit in terms of survival only in high-risk disease (i.e. stage Ic grade 3). Intermediate risk patients (i.e. stage Ib grade 3 disease), therefore, may be treated with adjuvant intravaginal brachytherapy alone to avoid the risk of side effects associated with pelvic irradiation. Overall, patients with clinically early endometrial cancer develop relapses in less than 20% of cases, mostly at distant sites. Randomized trials comparing adjuvant external pelvic irradiation versus adjuvant chemotherapy have shown conflicting clinical results. Chemotherapy seems to prevent or delay distant spread more than radiotherapy, while radiotherapy appears to prevent or delay local relapses more than chemotherapy, although these trends fail to achieve statistical significance. Recent evidence from a randomized trial indicates that sequential external pelvic irradiation with or without brachytherapy and platinum-based chemotherapy result in significantly better progression-free survival than radiotherapy alone in patients with high-risk endometrial cancer. Reliable surgical/pathological variables predictive of high risk of distant failure may be used to identify a subset of patients suitable for randomized trials of adjuvant chemotherapy with or without external irradiation.