Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non-cancerous neoplasia. During this period, numerous serum protein analytes have been investigated as alternative and/or supplemental tests for PSA, however in general these analytes have likewise suffered from a lack of specificity, often showing serum elevations in other clinical presentations. More recently, molecular assays targeting prostate disease at the DNA or RNA level have been investigated for potential diagnostic and prognostic utility. With the aid of modern genomics technologies, a variety of molecular biomarkers have been discovered that show potential for specific correlation with prostate cancer. Much of this discovery has been retrospective, using microdissected tissue from prostatectomy. The goal of current research is to apply genomic assays to noninvasive specimens such as blood and urine. Progress in this area is the subject of this review.