Prostate cancer (PCa) is the cancer most frequently diagnosed in older men and the second most frequent for incidence of all tumors. With the widespread use of serum prostate-specific antigen (PSA), the detection rate as well as the incidence of localized tumors has been increasing, thus leading to a drop in PCa-related mortality. However, a corresponding estimated rate of overdiagnosis as high as 50% has been reported, and the adverse side effects related to unnecessary treatments make the overall benefit of PSA mass screening unclear. The lower PSA threshold and extended prostate biopsy protocols have led to a marked increase of small, low-grade tumors that will never threaten a patient's survival. Sextant biopsy technique, extended biopsy protocols (12-18 cores) and saturation prostate schemes are already familiar terms, together with quantitative histology in the pathology departments. This brief review will try to focus on what usually is done and what should be improved in prostate needle biopsy in order to answer many critical points such as the clinical implication of different modalities of prostate biopsy (transrectal, transperineal or even targeted), the use of quantitative histology and the importance of the new molecular findings in addition to conventional histological parameters in the era of the active surveillance protocols.