Five to 10 percent of endometrial cancer (EC) patients are presented at advanced stage with a poor prognosis. There is no optimal treatment for stage III–IV EC. Combination of chemotherapy and radiation improved survival compared to monotherapy. Although the effect of combination treatment proves to be effective, optimal sequence of treatment is not clear. One approach is the sandwich method (three cycles of chemotherapy followed by radiation and then three more cycles of chemotherapy), other regimes are six cycles of chemotherapy followed by radiation (sequential treatment) or concomitant chemoradiotherapy. There are no randomized trials comparing these regimes but each has its own advantages and also some drawbacks. Either sandwich therapy or sequential regime seems to be reasonable approaches with similar oncologic outcome but sequential regime, particularly for stage IIIC2, is well tolerated with less toxicity and treatment breaks. Despite well-established combination therapies, prognosis of stage IIIC disease is still poor with a high rate of distant recurrences pointing out need for a better systemic therapy.