High-risk endometrial cancer (EC), only 15% of all EC cases, mainly affects elderly women, often with significant comorbid diseases. Because patients with high-risk EC are at increased risk of distant metastases and EC death, the use of adjuvant chemotherapy has been investigated in several trials. Trials comparing radiotherapy and chemotherapy have not shown survival difference. A first trial comparing combinations of chemotherapy and radiotherapy with radiotherapy alone suggested a progression-free survival benefit. Toxicity and quality-of-life data are lacking. The role of adjuvant chemotherapy for endometrial carcinoma remains unproven. High-risk EC remains the challenge for further research.