Prostate cancer is currently the most prevalent form of cancer in men and the second leading cause of can-cer death in the United States, and the third most common cancer in men worldwide. Increasing mor-tality rates due to prostate carcinoma have been ob-served worldwide. This disease usually progresses im-perceptibly; thus, patients are unlikely to seek medi-cal help during the early stages. For these reasons, screening programs aimed at early detection have been developed. The prostate-specific antigen (PSA) test is among the best screening tools available in medicine today and is recognized as the best marker for its early detection. Prostate cancers detected by DRE method alone are clinically localized only 50% to 60% of the time, whereas PSA-detected tumors are clinically localized 90% of the time and pathologi-cally confined to the prostate as determined at prostatectomy about two thirds of the time. Recently, the detection of localized prostate cancers has improved, owing to the development of various new biopsy methods. However, a standard biopsy method, including number of cores, has not yet been established at present. When screening results indi-cate the possibility of prostate cancer, a pathologic diagnosis may be pursued by ultrasound guided trans-rectal needle biopsy. Prostate biopsy is usually ad-vised if serum PSA is >4 ng/mL, and this procedure remains the gold standard for prostate cancer diagno-sis. Fine needle biopsy is less painful than core bi-opsy, but also less diagnostically accurate. Systematic biopsy protocols: In 1989, Hodge et al. coined the sextant biopsy method that is still the standard of reference in prostate cancer detection. The prostate is bilaterally divided into three regions (apex, midgland, and base), all of which are system-atically biopsied once. Although Hodge et al. first proposed sextant biopsy under transrectal ultrasound guidance, some recent reports have indicated that systematic sextant biopsy might be inadequate for cancer detection. In a standard transrectal ultrasonography (TRUS)-guided biopsy, a specimen is removed with a biopsy gun from any suspicious areas, followed by tissue cores from the base, mid-zone, and apical areas of the right and left lobes (sextant biopsy). However, de-pending on prostate volume, up to 18 cores can be obtained covering all prostate areas. Analysis of tumor histology using the Gleason grad-ing system provides some index of prognosis and may also guide local therapy. However, the sensitivity of the standard sextant biopsy may be suboptimal with false negative rates of approximately 20%. Accord-ingly, to further increase the diagnostic accuracy of prostate cancer, several investigators have recom-mended more extensive sampling of biopsy cores; however, there are several issues to be elucidated for establishing optimal biopsy strategy, such as the number and regions of biopsy cores to be taken. It has been reported that 20-30% of prostate cancers origi-nate the transition zone. Currently, it is well accepted that TRUS-guided transition zone biopsies are useful in patients exhibiting elevated serum PSA levels with an enlarged, non-nodular prostate and patients un-dergoing prior sextant biopsies. In general, the most common procedure for prostate cancer detection is the transrectal approach. Al-though the transperineal approach is not commonly used worldwide, some groups perform prostate biopsy using only this approach especially in European and Asian countries, but there are few data on transperin-eal prostate biopsy. Several studies have suggested that microvascularity is an essential requirement in the progression of prostate carcinoma. Trans-rectal ultrasound (TRUS)-guided systematic biopsy of the prostate is the standard technique for the diagnosis of prostate cancer. Tumors larger than 1 mm in diame-ter must form new blood vessels to grow larger. This neovascularity is expected to give rise to detectable flow using the Doppler principle. Focal peripheral zone hypervascularity at color Dop-pler ultrasonography is associated with an increased likelihood of prostate cancer or inflammation at bi-opsy, often without a focal gray-scale abnormality. Color Doppler ultrasonography may help identify an appropriate site for biopsy. A negative color Doppler ltrasonography scan, however, should not preclude biopsy, as color Doppler ultrasonography has a lim-ited sensitivity in the detection of all sites of cancer. Targeting of hypoechoic lesions Gray-scale imaging allows for an excellent anatomical delineation of the prostate gland in relation to the surrounding fat tis-sue, rectum, neurovascular bundles, and venous plex-us, as well as a clear division between the inner gland (transition and central zone) and outer gland (periph-eral zone) of the prostate. In the early 1980s, hypoechoic nodules were seen as the main presentation of prostate cancer, and solely these nodules were targeted at biopsy. The hypoechoic appearance is believed to be due to the increased microvessel density. However, up to 30% of all prostate cancers are isoechoic, and it is estimated that a hypoechoic nodule has a 17-57% chance of being identified as prostate cancer. Presently, in the PSA era, this percentage is reported to be as low as 9%. Contrast-enhanced US of the prostate with ultra-sound contrast agents can improve sensitivity for the detection of cancers in the outer gland, but it can also demonstrate focal enhancement in areas of benign hyperplasia. Contrast-enhanced transrectal ultrasonography im-proves the sonographic detection of malignant foci in the prostate. The performance of multiple biopsies of suspicious enhancing foci significantly improves the detection of cancer. The purpose of this review is to describe the various techniques of TRUS-guided prostate biopsy that are currently applied in radiological practice and to com-pare the diagnostic performance of systematic biopsy with imaging-guided techniques such as gray-scale, color, and power Doppler as well as contrast-enhanced imaging.