Bovine spongiform encephalopathy (BSE) has been documented in 28 countries and adversely affected farmers and rural communities around the world. Our study examines the impacts of and adaptive responses of producers to BSE in western Canada. Moreover, it explores the role that holistic management (HM), and its combined focus on environmental, social, and economic sustainability, might play in mitigating the effects of BSE. One survey was sent to 835 HM producers and another to 9,740 producers across Manitoba, Saskatchewan, and Alberta. The disease, and concomitant climate change and low commodity prices, had devastating impacts on both groups. Yet, HM producers were much more optimistic about their ability to adapt to BSE and the future of agriculture than their non-HM counterparts. Social networks, namely HM clubs and the larger HM community, enabled these producers to mitigate the impacts of BSE. Agronomic responses, especially those associated with rotational grazing and increases in on-farm biodiversity were also important. That HM has been such an effective adaptive response to BSE indicates the importance of this and other grassroots responses to rural crises, whether they be associated with zoonotic diseases or indeed environmental change as a whole.