High-grade prostatic intraepithelial neoplasia (PIN) is the earliest accepted stage in carcinogenesis, possessing most of the phenotypic and biochemical changes in cancer without invasion of the basal membrane of the acini. The support for high-grade PIN as the main premalignant lesion of prostate cancer is based on several lines of evidence derived from prostate cancer animal models, epidemiological, morphological, genetic, and molecular studies. The incidence of high-grade PIN averages 9% (range 4-16%) in prostate biopsies, representing 115,000 new cases of high-grade PIN diagnosed each year in the United States. Performing saturation prostate biopsies to rule out any coexistent prostate cancer followed by every 3-6 month serial repeated prostate biopsies is currently the only way in which to manage patients found to have high-grade PIN. Medical therapy for high-grade PIN may easily become the mainstay treatment for high-grade PIN. Treatment of high-grade PIN appears to be of clinical benefit notwithstanding the potential for prostate cancer risk reduction. These clinical benefits would reduce morbidity, enhance quality of life, delay surgery or radiation, and increase the interval for surveillance requiring invasive procedures.