Transrectal prostate biopsy is a pivotal procedure in urology, playing a central role in the diagnosis and management of prostate conditions, especially prostate cancer. This chapter provides a comprehensive overview of transrectal prostate biopsy, encompassing its clinical significance, advantages, and nuances. The transrectal approach offers accessibility, precision, and cost-effectiveness, contributing to its enduring popularity. Central to this technique are rigorous antiseptic procedures and local anesthesia, ensuring patient comfort and minimizing complications. The critical role of transrectal ultrasound (TRUS) guidance in real-time visualization and precise tissue sampling is underscored, particularly in the context of multiparametric magnetic resonance imaging (mpMRI) fusion biopsies, which enhance diagnostic accuracy. By merging mpMRI and TRUS, fusion biopsy minimizes the chances of missing clinically significant cases and fosters personalized treatment decisions. Despite its merits, transrectal prostate biopsy is not without complications, notably infection and bleeding, reinforcing the importance of patient counseling. This chapter delineates a multifaceted approach to infection control, encompassing antibiotic prophylaxis, rectal preparation, and advanced strategies like Betadine clisma. Through these comprehensive insights, this chapter serves as a valuable resource for healthcare providers and researchers, advocating for the continued significance and advancement of transrectal prostate biopsy in urological practice.