The cell cycle consists of a series of events that regulate cell life. The regulation and coordination result from a combination of several signals from different regulatory pathways which are activated in response to the presence of the right stimuli. Tumor suppressor genes represent a crucial milestone in the understanding of cancer genetics. The RB gene family includes three members: Rb/p105, p107 and RB2/p130. The regulation of all three members of the retinoblastoma family of proteins is complex and unique for each single member. Each member of the RB family of growth suppressive nuclear phosphoproteins elicits G1 growth arrest upon ectopic expression in sensitive cell lines, and their phosphorylation status is regulated in a cell cycle-dependent manner. In this review, we will discuss the role of Rb family members in the pathogenesis and prognosis of and their therapeutic impact on gynecological cancer.