Ovarian cancer is one of the most frequent solid tumor that shows clearly biphasic behaviour in response to chemotherapy, with the majority of patients who achieved complete remission after the first cycle of chemotherapy, and subsequently present a relapse which, in most cases, leads to death. Epithelial ovarian cancer (EOC) arises as a consequence of genetic alterations that affect the cells of the ovarian surface, which leads to changes that occur through the activation of oncogenes and inactivation of tumor suppressor genes. The progression of EOC is characterized by a series of combined epigenetic aberrations, including the most important of those determined by the loss of methylation of certain regions of DNA encoding genes such as Ras-association domain-containing family 1 [(RASSF1A) tumor suppressor], death-associated protein kinase [(DAPK) protein kinase associated with the regulation of apoptosis], human sulfatase- 1 [(hSulf-1) sulfatase, which plays a key role in the regulation of apoptosis], breast cancer 1 gene [(BRCA1) tumor suppressor gene, involved in the processes of DNA repair], and HOXA10 (gene required to promote many transcription factors). To date, accumulating evidence suggests that the initial clinical response is due primarily to the therapeutic efficacy of chemotherapy against differentiated cancer cells that constitute the bulk of the tumor, whereas the high rate of recurrence is thought to be due to remaining drug-resistant cells, biologically distinct, identified as cancer stem cells (CSC). Current efforts are focusing on genetic and cytological definition of CSC, to guide the development of new diagnostic, and therapeutic perspectives.