During the evaluation of prostate cancer, men who have undergone transrectal ultrasound-guided biopsy with negative results present a dilemma as to what further follow-up is required. Multiple variables have been proposed throughout the literature to improve cancer detection rates not only in initial biopsy results, but also on repeat evaluation. These variables include prostate-specific antigen (PSA) velocity, PSA density, free-percent PSA, and histological findings, each of which may singly or collectively dictate the need for further biopsy. After performing a Medline literature search using specific Medical Subject Headings (prostate biopsy, repeat prostate biopsy, PSA velocity, PSA density, free-percent PSA, prostate inflammation), we critically evaluated pertinent articles. Using this accumulated data and information, we composed an algorithm to assist in the decision process for repeat biopsy.