The dilemma of managing patients with chronic pelvic pain syndromes continues to frustrate physicians confronted with these complaints. Multiple diagnoses traditionally label this condition in men and women and, typically, implicate a pelvic-organ system when, in fact, very little objective evidence for a pathophysiologic process exists. Traditional therapies, consisting of antibiotics, anti-inflammatories, and muscle relaxants, simply do not work, and their lack of efficacy compared with placebo has been documented by randomized clinical trials in the US that were sponsored by the NIH. What do we do now? This review article attempts to describe the clinical efforts of several investigators and to put their patients' outcomes in perspective, and thereby suggest alternative therapies to help these patients.