This paper responds to claims that smallholders in the UK farming landscape present a biosecurity threat to commercial farming, by exploring smallholders’ perspectives on animal health and their practising of biosecurity, studied through focus group research in England. Biosecurity in animal agriculture has emerged as a key research theme, with attention paid to how biosecurity is both conceptualised and practised in different farming situations. Biosecurity, as an effort to make life safe, is viewed as an articulation of political and scientific discourses with on-farm practices and particular farming and food systems. The paper draws on recent theorisation of biosecurity to discuss smallholders’ engagement with the health of their animals and with biosecurity practices, and to explore their relationships with vets and commercial farmers. Contesting representations of themselves and their practices as bioinsecure, smallholders instead contend that commercial farmers and farming produce more risky disease situations, and that smallholding fosters relationships of care and response-ability more likely to engender animal health and welfare. At the same time, smallholders and farmers are involved in attempts to piece together a practical biosecurity under different pressures. The paper argues that within the complex topologies of heterogeneous farming landscapes, the ‘small scale’ of smallholding is constructed as problematic, and that there needs to be an acknowledgement of a politics of biosecurity in which different modes of practicing farming are debateable.