Conventional clinical and pathological parameters are limited in their capacity to detect patients with urothelial carcinoma of the bladder (UCB) who are at high risk for recurrence or mortality. The assessment of molecular biomarkers in surgical UCB specimens offers additional information on the biology of the disease, and might improve the prediction of oncologic end points. A wide range of candidate biomarkers, including key cell-cycle regulators, apoptotic markers and specific growth factors, have been reported to be of prognostic value. To date, however, no molecular biomarker for UCB has been introduced into clinical practice, mainly owing to insufficient validation and the absence of prospective studies. Knowledge about the value of molecular biomarkers in predicting the response to adjuvant or neoadjuvant therapies is also lacking. Prospective trials need to be initiated in high-risk patients selected on the basis of the expression patterns of molecular biomarkers that have already passed the initial steps towards clinical utility.