Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.