INTRODUCTION: Prostate biopsy strategies have greatly evolved over the past 2 decades. METHODS: We performed a literature review which addressed the initial and repeat biopsy schemes, pathologic risk factors for a positive repeat biopsy, and the ideal timing as well as the number of repeat biopsy sessions. RESULTS: Extended biopsy schemes (11-13 cores) should be used at initial and repeat biopsy. In the era of extended biopsy schemes, high-grade prostatic intraepithelial neoplasia no longer represents an independent predictor of prostate cancer on repeat biopsy. Conversely, the risk is appreciably increased with atypical small acinar proliferation, and its presence warrants a repeat biopsy, which may be performed as soon as the pathologic findings of the previous biopsy become available. Second and subsequent repeat biopsies carry a low detection yield. In most instances, the decision regarding the indications and the timing of a third or subsequent biopsy may be made after a 6 to 12 months interval following the repeat biopsy. CONCLUSION: Biopsy strategies and pathologic predictors of an increased risk of prostate cancer have appreciably changed over the past 2 decades.