An overview is given of the current conventional and contrast-specific transrectal ultrasound (TRUS) techniques for prostate imaging that may be used for guiding biopsy. Subsequently, a systematic literature search resulted in inclusion of four studies that directly compared systematic and contrast-enhanced-targeted TRUS-guided biopsy of the prostate. All four studies revealed that contrast-enhanced-targeted TRUS-guided biopsy significantly improved the positive biopsy core rate. In the largest study, the mean Gleason score of the contrast-enhanced-targeted TRUS-guided biopsies was significantly higher than that of the systematic biopsies. Future randomized clinical trials, preferably in a non-academic multi-institutional set-up, will have to be performed to confirm the value of contrast-enhanced-targeted TRUS-guided biopsy in regular clinical practice.