Throughout the past century, we have refined our understanding of prostatitis, moving from using a primarily clinical definition to considering it as a complex inflammatory condition. The inconsistency in identifying uropathogens in patients with symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has led to controversy in therapeutic management. There is compelling evidence that the normal prostate has minimal inflammation and no bacteria. Clinicians using the Meares/Stamey criteria identified uropathogens localized to the prostate in only 6% to 8% of CP/CPPS patients. This suggests that bacteria may have a role in less than 10% of men with CP/CPPS. That some patients respond to antimicrobials could suggest that eradication of bacteria reduces symptoms. However, the beneficial effect of antimicrobial drugs may not be due to their antibacterial action, but to their anti-inflammatory action. The normal prostate shows minimal inflammation, but only 50% of CP/CPPS patients exhibit prostatic leukocytosis. Prudence demands that we examine the function of the white blood cells--the cytokines produced. Several basic science advances allowed new avenues of research regarding the detection of molecular evidence of causative uropathogens. New research brings new controversy and unexpected findings, but further refines our understanding of the immune system and the CP/CPPS disease process.