Inappropriate use of antimicrobials is linked to the development and spread of drug-resistant pathogens and is associated with increased morbidity, mortality, lengths of hospital stay, and health care costs. "Antimicrobial stewardship" is the umbrella term for an evidence-based knowledge translation strategy involving comprehensive quality improvement activities to optimize the use of antimicrobials, improve patient outcomes, reduce the development of antimicrobial resistance and hospital-acquired infections such as Clostridium difficile, and decrease health care costs. To assess the perceptions and experiences of antimicrobial stewardship program leaders in terms of clinicians' attitudes toward and behaviours related to antimicrobial prescribing. In this qualitative study, semistructured interviews were conducted with 6 antimicrobial stewards (2 physicians and 4 pharmacists) at 3 academic hospitals between June and August 2013. The following 3 key themes emerged from the interviews: getting the right people on board, building collegial relationships, and rapidly establishing a track record. The study results elucidated the role and mechanisms that the program leader and other antimicrobial stewards used to influence other clinicians to engage in effective utilization of antimicrobials. The results also highlighted the methods employed by members of the antimicrobial stewardship team to tailor their strategies to the local context and to stakeholders of participating units; to gain credibility by demonstrating the impact of the antimicrobial stewardship program on clinical outcomes and cost; and to engage senior leaders to endorse and invest in the antimicrobial stewardship program, thereby adding to the antimicrobial stewards' credibility and their ability to influence the uptake of effective antimicrobial use. Collectively, these results offer insight into processes and mechanisms of influence employed by antimicrobial stewards to enhance antimicrobial use among clinicians, which can in turn inform future implementation of antimicrobial stewardship and strategies for organizational change in hospitals.