Prostate biopsy (PBx) techniques have significantly changed since the original Hodge's ‘sextant scheme’, which should now be considered obsolete. The feasibility of carrying out a biopsy scheme with a high number of cores in an outpatient setting is a result of the great improvement and efficacy of local anesthesia. Peri-prostatic nerve block with lidocaine injection should be considered the ‘gold standard’ because it provides the best pain relief to patients undergoing PBx. The optimal extended protocol should now include the sextant template with an additional 4–6 cores directed laterally (anterior horn) to the base and medially to the apex. Saturation biopsies (i.e. template with ≥20 cores, including transition zone) should be carried out only when biopsies are repeated in patients where there is a high suspicion of prostate cancer. Complementary imaging methods (such as color- and power-Doppler imaging, with or without contrast enhancement, and elastography) could be used in order to increase the accuracy of biopsy and reduce the number of unnecessary procedures. Nevertheless, the routine use of these methods is still under evaluation.