© 2015 European Association of Urology. Context: Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. Objective: To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response. Evidence acquisition: Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. Evidence synthesis: An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. Conclusions: Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. Patient summary: We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests. Personalized genetic profiling of primary and metastatic tumor cells is available for routine clinical decision making. Greater understanding of the potential long-term benefits and limitations of these tests and their optimal use in clinical decision making is important.