Endometrial cancer is the seventh most common malignancy among women worldwide. Despite most cases being diagnosed at an early stage, the death rate has increased steadily over the past 20 years. The lack of an effective, standardized adjuvant treatment for women at a high risk of recurrence has contributed to these disappointing results. The goal of this review was to assess the role of hormonal and cytotoxic therapies in the adjuvant treatment of endometrial cancer. Once defined, an evidence-based management algorithm for this neoplasm was proposed. A thorough literature search was undertaken using the Cochrane and Pubmed databases. Systematic reviews, meta-analyses, and randomized controlled trials were first collected and critically analyzed. Other study types were secondarily considered when pertinent. The choice of the adjuvant therapy in early-stage endometrial cancer must be a patient-specific decision. Preliminary data suggest a role for chemotherapy in high-risk subgroups. However, further research is necessary to confirm this. To date, hormonal therapy has not been widely used in the management of early-stage disease, other than for conservative treatment in a fertility-sparing setting. Both hormonal and chemotherapy represent valuable therapeutic tools for the management of patients affected by advanced disease.