The aim of this review is to provide a contemporary outline of our current understanding of the molecular and genetic events associated with tumorigenesis and the progression of bladder cancer. A comprehensive review of the literature was performed on the molecular alterations associated with transitional cell carcinoma (TCC) of the bladder. Intense research efforts are being made to better identify and characterize various bladder cancers and their true biologic potential. The need to predict which superficial tumors will recur or progress, and which invasive tumors will metastasize has led to a much better understanding of the molecular pathways associated with bladder cancer. The molecular changes that occur in TCC of the bladder are numerous and can be categorized into: (1) chromosomal alterations leading to carcinogenesis, (2) loss of cell cycle regulation accounting for cellular proliferation, and (3) metastasis, guided by events such as angiogenesis. It is becoming apparent that the accumulation of genetic and molecular changes ultimately determines a tumors phenotype and subsequent clinical behavior. At the present time, conventional histopathologic evaluation of bladder cancer (tumor grade and stage) is inadequate to accurately predict the behavior of most bladder tumors. While new laboratory techniques have allowed us to better understand how bladder cancer develops and ultimately progresses, few of these techniques are currently available for use in the clinical setting. The ultimate goal is to develop reliable prognostic markers which will accurately predict not only the expected clinical course of an individual bladder tumor but also the response of that tumor to currently available therapies. More importantly, this information may be employed in the future to dictate altogether new treatments for the prevention and/or stabilization of the early molecular events that lead to the development of bladder cancer.