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Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression, and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by the conventional clinical and pathological parameters. None of the biomarkers reported to date have shown sufficient sensitivity and specificity for detecting the whole spectrum of bladder cancer diseases in routine clinical practice. The limitations of established prognostic markers requires us to identify better molecular parameters that could be of interest in predicting the prognosis of bladder cancer patients, in particular, the high-risk patient groups that are at risk of progression and recurrence. Recent progress in epigenetic modification and gene silencing opened a new avenue for the identification of epigenetic markers, which appears to be more useful for cancer diagnosis and prognosis. Although epigenetic markers also have limitations, the combined epigenetic marker approach may increase sensitivity and reliability. The epigenetic silencing of tumor-suppressor genes is interesting from a clinical standpoint because of the possibility of reversing epigenetic changes and restoring gene function in a cell. In addition, microarray technology provides us with additional tools for the analysis of global gene-expression analysis of tumor samples. Future microarray analyses are likely to reveal particular gene-expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as a patient's survival and responsiveness to different anticancer therapies, with great specificity and sensitivity. (Cancer Sci 2008; 99: 646–652)