High-grade prostatic intraepithelial neoplasia (HGPIN) is a premalignant lesion associated with increased risk of coexistent cancer or delayed progression to carcinoma. Extended biopsy schemes have improved the ability to rule out concurrent cancers, increased the detection of isolated HGPIN and removed the routine necessity for immediate repeat biopsy. As the natural history of HGPIN is poorly defined, and no non-invasive marker allows monitoring of progression to cancer, routine delayed interval biopsy should be considered in all patients. In this article, we present an overview of the existing literature on HGPIN and a proposed strategy for clinical management.