Background & Purpose: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) negatively impacts on quality of life and sexual function in men of all ages. Typical treatment of antibiotic and anti-microbial drugs is not often successful. The purpose of this case report is to describe manual trigger point release as the primary physical therapy intervention for two patients who were unsuccessfully treated with the biomedical model of prescription drug therapies. Case Description: Two men ages 45 and 53 diagnosed with chronic prostatitis were referred to physical therapy following unsuccessful medicinal treatment. The patients were treated with myofascial trigger point release and instructed in progressive muscle relaxation, flexibility exercises and aerobic exercises. Outcomes: Changes in the patients' National Institutes of Health Chronic Prostatitis Symptom Index revealed differences between pre and post intervention scores reflecting decreased pain and improved quality of life. One patient reported a 100% reduction of all symptoms. His score improved from 25 (43 total possible) pre intervention to 0 post intervention. The other patient reported an 8 point reduction in the total score which is considered clinically significant. His score improved from 29 pre intervention to 21 post intervention. Discussion: Manual trigger point release therapy performed by a physical therapist along with progressive muscle relaxation, flexibility exercises, and aerobic exercises appeared to be beneficial to both patients in reducing pain and improving sexual function. Manual trigger point release should be considered as a primary treatment for CP/CPPS.