Among genitourinary malignancies, bladder cancer is a common, potentially dangerous and exceedingly costly disease entity. Predicated on substantial gains in our understanding of the natural history and molecular biology of bladder cancer, recent years have seen an explosion of new applied technologies to aid clinicians in the management of bladder cancer. Herein we present a systematic overview of general conceptual issues and specific strategies of potential relevance to the clinical evaluation of patients with bladder cancer. A number of basic epidemiological issues provide the relevant background within which we should consider candidate biomarkers. Within this framework, we highlight a number of important recent research findings representative of the large number of candidate bladder cancer biomarkers that have emerged. With several markers already having obtained regulatory approval for clinical use, this topic is of clear relevance not only to researchers but also to the practicing physician. Bladder cancer is a common, costly, and potentially dangerous disease with the opportunity for significant technological inroads in the area of applied biomarkers. An appreciation of basic epidemiological considerations informs our consideration of the state of the art and identifies specific strategies amenable to further innovation.