Introduction: This article reviews the rationale and data supporting alpha blocker therapy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the most common and difficult prostatitis syndrome. Methods: Systematic review identified ten clinical trials evaluating alpha blocker therapy for patients with CP/CPPS, including five open-label or small prospective studies and five double-blinded and placebo-controlled clinical trials. Results: Encouraging results in uncontrolled and small clinical trials led to the development of reasonably powered, double-blinded, placebo-controlled, randomized clinical trials evaluating terazosin, doxazosin, tamsulosin, and alfuzosin. Conclusions: Current data suggest that treatment-naïve and/or newly diagnosed patients appear more likely to respond than long-term, chronic refractory patients. Longer courses of treatment (12 weeks to 6 months) appear superior to shorter courses, and less selective agents appear superior to more selective alpha 1 blockers. These observations outline important questions that must be answered to define optimal treatment strategies for patients with CP/CPPS.