Urothelial carcinoma of the bladder exists as a spectrum of clinical states ranging from non-muscle-invasive to muscle-invasive to advanced/metastatic disease. Each clinical state is associated with a unique tumor biology, prognosis, and approach to treatment. The field of personalized medicine offers the promise to individualize therapeutic decisions in each clinical state with the goal of preventing or delaying progression to more advanced disease states while optimizing quality of life. This review will discuss bladder cancer as a paradigm for the development of personalized cancer medicine, focusing on recent efforts, current challenges, and future opportunities.