The current recommendation in patients with a clinical suspicion for prostate cancer is to perform systematic biopsies extended with targeted biopsies, depending on mpMRI results. Following a positive mpMRI [i.e. Prostate Imaging Reporting and Data System (PI-RADS) ≥3], three targeted biopsy approaches can be performed: visual registration of the MRI images with real-time ultrasound imaging; software-assisted fusion of the MRI images and real-time ultrasound images, and in-bore biopsy within the MR scanner. This collaborative review discusses the advantages and disadvantages of each targeting approach and elaborates on future developments. Cancer detection rates seem to mostly depend on practitioner experience and selection criteria (biopsy naïve, previous negative biopsy, prostate-specific antigen (PSA) selection criteria, presence of a lesion on MRI), and to a lesser extent dependent on biopsy technique. There is no clear consensus on the optimal targeting approach. The choice of technique depends on local experience and availability of equipment, individual patient characteristics, and onsite cost-benefit analysis. Innovations in imaging techniques and software-based algorithms may lead to further improvements in this field.