Misuse of antibiotics in hospitals in Australia and internationally is common. The combination of multi-resistant organisms and continued misuse of antibiotics is contributing to a predicted ‘antimicrobial perfect storm’ in the coming decades. Attempts to influence doctors’ use of antibiotics have seen limited success internationally, yet few studies have explored the potential social factors driving current practices within hospitals and the interpersonal processes that underpin persistent ‘suboptimal’ antibiotic use. In this qualitative study of hospital-based Australian doctors we explore some of these dynamics including: the role of clinical uncertainty and ambivalence; experiences of immediate risk; interpersonal and intra-professional pressure; and the role of localised norms and ‘craft groups’ in driving antibiotic practices. We argue that the development of a sociological understanding of antibiotic misuse in the hospital sector (and beyond) is vital for progress to be made in protecting antibiotics for future generations.