Transrectal ultrasound-guided biopsy of the prostate is the gold standard for the detection of prostate cancer. In its current form, transrectal gray-scale ultrasound is unable to differentiate malignant prostate tissue from benign tissue. The general indications for performing a sonographic guided biopsy of the prostate are an abnormal digital rectal examination or an abnormal prostate-specific antigen (PSA). Several controversial areas remain: the ideal number of biopsy cores, the use of PSA velocity, free PSA, PSA density, age- and race-adjusted PSA, the use of local anesthetics, and the overall best patient preparation methods, including such topics as routine antibiotic prophylaxis or bowel enemas, remain unsettled. There are also unanswered questions regarding repeat biopsy and protocols for managing patients with a diagnosis of high-grade intraepithelial neoplasia. This article will explore some of the current controversies and review the pertinent literature.