Prostate cancer (PCa) is the most commonly diagnosed male cancer in the United States. The prostate-specific antigen (PSA) biomarker has been widely used to screen men for prostate cancer. Challenges of PSA cancer-specific sensitivity and specificity exist; fortunately, a new generation of PCa biomarkers is emerging, consisting of serum-, urine-, and tissue-based assays that may supplement PSA testing, or replace it over time.The identification and development of these biomarkers have been facilitated, in large part, by new genomic technologies that have enabled an additional interpretation of the individual patient's tumor biology. Several biomarkers with specific indications for disease diagnosis, prediction, prognosis, and therapeutic response are now commercially available. Furthermore, genomic assays may now stratify the risk of aggressive PCa at the time of diagnosis. In this article, we review recent advances in the discovery of PCa biomarkers, their integration into clinical practice, and implications for improving clinical management of the disease.