This paper explores the progress and challenges associated with the application of organizational factors and approaches to infection prevention and control (IPC) and antibiotic stewardship (AS) in England, many of which have been considered and supported by the Advisory Committee on Antimicrobial Resistance and Healthcare-associated Infections (ARHAI). An organizational perspective is described and the wider macro context and socio-political forces that shape an organizational approach are considered. Factors that drive organizational change in IPC and AS are discussed. The tensions, constraints and dilemmas that can occur are identified and outstanding challenges are debated. Some recommendations for the future direction of IPC and AS organizationally focused strategies and research are proposed.