Prostatitis reflects a broad spectrum of prostatic infections, both acute and chronic. Chronic prostatitis, known as National Institutes of Health category III or chronic pelvic pain syndrome, broadly defines a disease that is still poorly understood, and as a consequence, difficult to treat. Typical symptoms include pelvic pain and voiding dysfunction. Infection is often cited as the cause of this condition, despite frequent negative cultures. A close look at the local prostatic microenvironment may yield clues. The role of inflammatory mediators and what stimulates them can point to potential sites of prevention. A genetic link or relationship to other diseases may prove to be part of the cause. Furthermore, a neurologic source, whether anatomic or psychologic, has been strongly debated. Ultimately, it may become clear that chronic prostatitis represents the final common result of a disease that originates from a cascade of multiple stimuli.