Intra-observer variability in defining clinic-pathologic risk factors and the heterogeneity of outcomes has led to challenges in defining the optimal management for endometrial cancer (EC) patients. The Cancer Genome Atlas identification of four distinct molecular subgroups has greatly enhanced our understanding of the biology of EC. Integration of histo-molecular information provides more accurate characterization of disease subgroups and prognosis. This facilitates prognostication and optimization of adjuvant therapy decisions, avoiding the potential for both under and over treatment. Molecular profiling also delivers the potential to predict therapy response and define the optimal approach for a given disease subtype in both adjuvant and recurrent disease settings. We can also more accurately to identify patients and families with Lynch syndrome and institute risk reducing measures. Molecular profiling facilitates more precise and accurate management of our patients with EC and it should become integrated into routine care.