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Antibiotic usage has been a growing concern in both human and veterinary medicine in recent years as resistant bacteria appear to be an increasingly widespread problem in all species. Conversely, the development of new antibiotics has slowed, leaving both doctors and veterinarians with a finite number of options for treating microbial infections. Particular challenges surround the use of antibiotics in small mammals, such as species-specific sensitivities to certain drugs and the limited range of licensed products available. This article will outline factors affecting antibiotic selection in small mammals and discuss approaches to common presentations.