Over 1 million men undergo biopsy in the United States each year to evaluate for prostate cancer (S. Loeb, H. B. Carter, S. I. Berndt, W. Ricker, and E. M. Schaeffer, J Urol 186:1830–1834, 2011,http://dx.doi.org/10.1016/j.juro.2011.06.057). In recent years, there has been a rise in infectious complications related to these procedures. This review aims to provide an overview of the guidelines that direct transrectal prostate biopsy, to describe associated infection, and to evaluate the published data driving the current trend toward prebiopsy screening for resistant organisms.