Localized prostate tumors have various clinical, biological and histopathologic characteristics that lead to different progression profiles. High-risk, clinically localised disease has been classically defined by clinical examination, PSA levels and histopathologic data. High-risk localized prostate tumors have usually a worse outcome, but classic stratification predictive of outcome for prostate cancer is a matter of debate concerning its accuracy. Diagnosis of high-risk prostate cancer has been improved by the use of MRI for local extension and risk of metastases. Pet-scan shows promising results for lymph node metastasis detection. Bone scan is widely used, as recommended. Optimal treatment for these men is the combination of androgen deprivation therapy and radiation therapy, although surgery can be used in some cases. Recent and major advances in the field of molecular biology are expected to provide new tools to better stratify men with prostate cancer at diagnosis. Indeed, numerous biomarkers are in development, as a consequence of a better comprehension of molecular basis of prostate cancer. New biomarkers (including circulating tumor cells) and genetic variations associated with prostate cancer aggressiveness should help us to define more precisely high-risk disease. Endly, these data should help to determine predictive factors for individual treatment response and indications, leading to an individualized management by targeted therapies.