Ovarian cancer is the fourth most common cancer in women and the most lethal gynecological malignancy. The high mortality rate is attributable to the asymptomatic nature of the early stage of the disease, the lack of reliable screening tests, and the development of drug resistance. Approximately 90% of ovarian cancers are thought to originate from the ovarian surface epithelia (OSE). Development of in vivo experimental models that accurately recapitulate genetic events that occur during human epithelial ovarian cancer (EOC) initiation and progression is crucial for a better understanding of EOC pathogenesis, identification of early disease markers, and development of more effective therapy. Historically, one of the most challenging problems in developing genetically engineered mouse models (GEMMs) of EOC has been the lack of tissue-specific promoters that regulate transgene expression exclusively in adult OSE cells. Recent improvements in gene delivery technology have greatly accelerated development of GEMMs of EOC. This unit describes two distinct methods of transforming OSE cells in GEMMs and the potential applications of these models in oncology drug discovery and development.