Prostate cancer is the most common malignancy in men, with an estimated 268,490 new cases in the United States in 2022, and 12,500 new diagnoses annually within the Veterans Health Administration (VHA). A major challenge for prostate cancer management is identifying patients who would benefit from treatment and tailoring the intensity of that treatment to personalized risk assessments. Risk stratification traditionally has been based on readily available clinical features; however, multiple options exist for treatment, and there is variability in patient outcomes not otherwise explained by currently recognized risk factors. Individualized prognosis beyond clinically based risk stratification schemas could inform patient-physician decisionmaking, reduce unnecessary overtreatment, and improve patient outcomes. A relatively recent advancement in prostate cancer risk stratification is the development of commercially available, tissue-based genomic classifiers. This systematic review addresses the impact of 3 commercial genomic classifier tests—Decipher, Oncotype DX GPS (now named Genomic Prostate Score but referred to in this report as Oncotype), and Prolaris—on risk classification, treatment choice and harms, and the prognostic ability of these tests beyond the clinical features of patients diagnosed with or treated for localized prostate cancer. (See Appendix A for guidelines for the 3 tests.)