Current treatments for advanced endometrial cancer are chemotherapy or hormonal therapy. This chapter describes the molecular genetic alterations associated with hereditary and sporadic endometrial carcinomas and explores potential treatment strategies arising from this knowledge. In approximately 5-10% of endometrial carcinoma cases there is an inherited predisposition to cancer. Classically, endometrial cancer has been categorised into two groups based on clinical and histopathological features: type I (endometrioid) and type II (non-endometrioid) endometrial carcinoma. The identification of activating mutations in FGFR2 in endometrioid endometrial cancers provides a potential theraputic target. Pre-clinical studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to the pan-FGFR inhibitor PD173074. Future clinical trials should explore the role of PTEN as a synthetic lethality target for PARP inhibitors in endometrial cancer. Other potential strategies include targeting FGFR2 and microsatellite instability (MSI).