The staggering advances in genetics and genomics achieved following the completion of the human genome project have deeply impacted clinical management and diagnostics in solid tumor oncology. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives to improve upon the so far modest outcome in muscle invasive bladder cancer patients is evident. Well-validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management are lacking. Identifying robust predictive biomarkers that will stratify response to emerging targeted therapeutics is another crucially needed development. The following is an overview of the molecular pathways involved in bladder cancer oncogenesis with a focus on promising candidate biomarkers that may soon make their transition to the realm of clinical management of urothelial carcinoma.