Urologic chronic pelvic pain syndrome (UCPPS) is a symptom-based umbrella term for interstitial cystitis/painful bladder syndrome (IC/PBS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men. Unfortunately, no gold standard for diagnosis or treatment of UCPPS exists. We review several emerging theories on the etiology and pathogenesis of UCPPS with a special emphasis on genomic and proteomic technologies. We also propose a systems-biology approach to elucidating the pathogenetic mechanisms implicated in UCPPS and the discovery and validation of new biomarkers for UCPPS. Using data gleaned from high-throughput genomic and proteomic screens can help develop effective treatments for this enigmatic chronic pelvic pain syndrome.