Cancer is a genetic disease, and inherited or acquired genetic defects contribute to the initiation and progression of cancer. Improved molecular techniques have lead to the identification of many of these genetic mutations in gynecologic malignancies. The molecular characterization of cancer has provided a better understanding of tumor formation and the clinical behavior of different tumor types, with important implications for developing screening tests and prognostic markers. Applications of these findings have led to novel targeted gene therapies that correct the critical genetic defects seen in gynecologic cancers. Future research will focus on the clinical translation of these genetic alterations as targets of cancer prevention, screening, and treatment.