The introduction of multiparametric magnetic resonance imaging (mpMRI) has allowed doctors to direct prostate biopsies toward suspicious lesions rather than randomly. This chapter focuses on targeted biopsy based on MRI/ultrasound (US) fusion software, describing its main features, indications, and performance compared to other sampling methods. The acquisition and reporting of magnetic resonance by the radiologist constitute the initial step of the procedure. Various fusion devices enable the alignment of pre-biopsy magnetic resonance (MR) images with intraoperative transrectal US to enable the urologist to perform a targeted biopsy directed toward MR-visible lesions. Targeted biopsy based on MRI/US fusion software is indicated as a frontline approach in cases of suspected prostate cancer (PCa). Some studies have compared targeted biopsy based on MRI/US fusion software with standard biopsy, concluding that targeted biopsy appears to identify an equal or greater number of men with clinically significant PCa compared to standard biopsy. The in-bore MRI biopsy still requires further studies. In conclusion, the targeted approach based on MRI/US fusion software seems to have valuable features to be added to the standard diagnostic pathway of PCa for achieving accurate risk stratification.