For men diagnosed with early stage prostate cancer a critical need exists for molecular assays that accurately distinguish aggressive prostate cancer from those cancers that will not cause harm if left untreated. In this project, we assessed three different panels of established molecular biomarkers for their ability to distinguish aggressive cancers from indolent cancers. We established agreements with three commercial companies to analyze their biomarker platforms in our multi-center, prospectively accrued prostate cancer active surveillance cohort the Canary Prostate Active Surveillance Study (PASS). We evaluated three biomarker panels in tissue (GHIs OncotypeDX), blood (OPKOs 4K Score), and urine samples(Hologic/GenProbes PCA3) with well annotated clinical and pathologic data collected as part of PASS. We conducted rigorous statistical evaluation to demonstrate the utility and performance of biomarkers in clinical practice to predict aggressive disease. The accuracy of each biomarker for predicting short- and long-term progression has been characterized with time dependent receiver operating characteristic curves. The successful clinical validation of biomarkers that offer substantially improved predictive and prognostic accuracy should bring extraordinary potential to improve the care of prostate cancer patients.