Antimicrobial stewardship programs (ASPs) are a key national initiative to promote appropriate use of antibiotics and to reduce the burden of resistance. The dilemma of managing the outlier physician is especially complex. We outline strategies to establish a successful ASP that reviews appropriate efforts to achieve the goal of modifying outlier physicians’ behavior. One must try to differentiate deviation from ASP norms from all other issues of outliers. Essential elements include identifying and understanding the local problems, planning, and achieving hospital administration and medical staff support. A successful ASP includes effective communication and acceptance of evidence-based recommendations, so that patient clinical outcomes will be optimized.