The determination of prognosis in bladder cancer is currently based on staging methods that rely primarily on the pathological stage of a tumor with limited objective correlates. The development and progression of bladder cancer involve alterations in several cellular pathways. Dysregulation in markers associated with cell-cycle regulation has been the most extensively examined molecular aberration in this cancer. Individual alterations of these markers have been associated with disease outcome, with several observations suggesting that their prognostic potential is independent of pathological stage. While many individual molecules in the cell growth receptor signaling, p53, and retinoblastoma (Rb) pathways have been identified, there is a general lack of consensus on which markers can be adopted in the clinical setting. More recent studies have suggested that the combination of markers as concise panels may be more beneficial in determining the degree of aggressiveness of a given tumor and its impending outcome than individual markers alone. This review will discuss alterations in molecules within pathways controlling cell-cycle regulation in the context of bladder cancer, and their impact on patient outcome when examined individually and in combination.