AbstractEndometrial cancer is the most common gynecological malignancy in high‐ and middle‐income countries. Although the overall prognosis is relatively good, high‐grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo‐oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node‐positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I–II patients with high‐risk factors and Stage III patients; chemotherapy is especially used in non‐endometrioid cancers and those in the copy‐number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease‐free interval.