The purpose of this review is to analyze clinical evidence about the activity and efficacy of anthracycline-based chemotherapy in metastatic endometrial cancer and to identify the most important preclinical findings that would address future clinical trials. A literature search of published studies was undertaken. Studies were selected by predefined criteria. Clinical trials and preclinical studies were analyzed. The search identified eight phase 3 and 13 phase 2 clinical trials of patients with metastatic endometrial carcinoma treated with an anthracycline-based regimen. The planned dose intensity of the anthracycline had no effect on response rates and survival. Survival increased for patients with a good performance status, and sometimes the duration of responses to anthracycline monotherapy can be very long-lasting. The major findings of anthracycline resistance in preclinical models are reported. Possible future biomarkers targeting mechanisms of anthracycline resistance are suggested, and efforts to define a molecular classification of endometrial cancer are desirable.