Urology practice guidelines recommend active surveillance as the standard of care for the management of favorable-risk (grade group 1) prostate cancer, as well as for some selected cases of intermediate-risk (grade group 2) disease. Active surveillance programs rely on sequential assessments, namely PSA tests, biopsies, and magnetic resonance imaging (MRI), to detect progression to higher-grade prostate cancer in a timely manner. Historically, transrectal prostate biopsies have been the gold standard; in recent times, however, considering that transperineal biopsies are associated with less infectious complications, many institutions are increasingly leaving transrectal in favor of transperineal biopsies. In the context of active surveillance, it has been demonstrated that transperineal biopsies are associated with a higher detection rate for progression, plausibly because of the enhanced ability to sample the anterior aspect of the prostate. Irrespective of the biopsy approach, active surveillance protocols typically require performing an MRI prior to the biopsy and repeating such assessments every 2–3 years. In this chapter, we will review the historic landscape of prostate biopsies, and we will put them in the context of active surveillance.