This review describes the transrectal ultrasound (TRUS) features of prostate cancer (PC), discusses the role of TRUS in the detection of PC and defines the modalities of biopsies in patients with suspected PC, particularly concerning prevention of complications, the number of biopsies and the biopsy schemes ensuring an optimal cancer detection rate. TRUS alone has limited potential to identify PC because of frequent multifocality of cancer within the prostate, the variable sonographic appearance of prostatic tumors, the poor specificity of focal US abnormalities, and the substantial percentage of isoechoic PC. Over the past decade, the sextant biopsy technique has emerged as the standard of care in the detection of PC. However, limitations in cancer detection have been appreciated, particularly a false-negative rate approaching 20%. This high failure rate has led investigators to refine biopsy techniques to improve cancer detection and to increase the total number of cores. Currently, recommendations include increasing the biopsy number to a minimum of 10-12 cores, including sampling of the lateral prostate. Refinements in imaging technologies (power Doppler sonography, microbubble intravenous sonographic contrast agents, and MR spectroscopy or dynamic contrast MR imaging) should eventually improve targeting of prostate needle biopsy and reduce false-negative biopsies.