Overcoming intrinsic and acquired chemoresistance is the major challenge in treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond favorably to chemotherapy, but subsequently the majority gain acquired resistance resulting in recurrence, cancer dissemination and death. This chapter summarizes recent advances in our understanding of the cellular origin and the molecular mechanisms defining the basis of cancer initiation and malignant transformation with respect to epithelial-mesenchymal transition (EMT) of ovarian cancer cells. We discuss the critical role of EMT frequently encountered in different phases of ovarian cancer progression and its involvement in regulating cancer growth, survival, migration, invasion and drug resistance. Using model ovarian cancer cell lines we highlight the relationship between EMT and the ‘cancer stem cell (CSC)-like phenotype’ in response to drug treatment, and relate how these processes can impact on chemoresistance and ultimately recurrence. We propose the molecular targeting of distinct ‘EMT transformed CSC-like cells’ and suggest ways that may improve the efficacy of current chemotherapeutic regimens much needed for the management of this disease.