Antimicrobials have been used in excess for decades. As a result, antimicrobial resistance and cost have increased. In response to this growing national problem, hospital antimicrobial teams were recom-mended in 1988, but few institutions have invested in comprehensive, interdisciplinary programs. The division of infectious diseases at the University of Louisville School of Medicine was a leader in 1990 by establishing an antimicrobial team at the University of Louisville Hospital and Veterans Affairs Hospital. This manuscript reviews the activities of the antimicrobial teams to create antimicrobial guidelines, evaluate antimicrobial use, and provide feedback to physicians. It also summarizes the successful impact the teams have had on optimizing antimicrobial use in the hospital by improving compliance with the guidelines, controlling resistant organisms, and preventing escalation of antimicrobial cost over the years.