Individualizing treatment recommendations for men with a diagnosis of prostate cancer remains a major challenge for clinicians. These challenges occupy many clinical scenarios ranging from newly diagnosed disease localized to the prostate to biochemically recurrent disease in the postprostatectomy setting, and in the distant metastatic settings. To date, clinical decision-making has largely rested on traditional clinicopathologic features, including Gleason grading, T stage, prostate-specific antigen (PSA) levels, margin status, lymph node involvement, and imaging. However, at best, these measures serve as incomplete surrogates for the actual underlying biology driving the behavior of the disease in each patient. Direct interrogation of biologic features of tumors (for example, in the form of gene expression assays) has been shown to provide superior prognostic accuracy over standard clinicopathologic features across several cancer types.