Concern over the spread of infectious animal diseases has led to attempts to improve the biosecurity behaviour of farmers. Implicit within these behavioural change strategies are different geographies of knowledge that enact different versions of disease. Some versions are fixed whilst others attempt to live with disease by accommodating difference. This paper explores how these different strategies fare in attempts to promote biosecurity to farmers. The paper compares farmers' responses to ‘high-risk’ and ‘population’ strategies of biosecurity behaviour change in relation to bovine tuberculosis in cattle. Drawing on quantitative assessments of biosecurity and farmer interviews, the paper suggests that biosecurity behaviour change initiatives that draw on locally situated practices and knowledges of disease are more likely to have an impact on biosecurity behaviour than those which attempt to standardise biosecurity and disease. Through a process of constant tinkering and rewiring biosecurity to fit local social and ecological conditions, approaches like the high-risk strategy represent one way of living with the uncertainties of disease. It is argued that thinking more broadly about the nature of disease should lead policymakers to re-evaluate the purpose of disease control and their approaches to it.