The growing global concern around antimicrobial mis-use and proliferating resistance has resulted in increasing interest in optimising antibiotics, particularly in hospitals. While the agenda to tighten antibiotic use has been critically explored in metropolitan settings, the dynamics of rural and remote settings have remained largely unexplored. Drawing on 30 interviews with doctors, nurses, and pharmacists in a remote Australian hospital, we focus on the pertinence of setting, and its importance for contextualising and potentially achieving antibiotic optimisation. Building on previous work on the dynamics of locale and core-periphery relations, here we consider how antimicrobial practice is deeply embedded in experiences of being on the geographical periphery, and crucially, at the periphery of (established) knowledge.