This paper elaborates a ‘pathways approach’ to addressing the governance challenges posed by the dynamics of complex, coupled, multi-scale systems, while incorporating explicit concern for equity, social justice and the wellbeing of poor and marginalised groups. It illustrates the approach in relation to current policy challenges of dealing with epidemics and so-called ’emerging infectious diseases’ such as avian influenza and haemorrhagic fevers, which involve highly dynamic, cross-scale, often-surprising viral–social–political–ecological interactions. Amidst complexity, we show how different actors in the epidemics field produce particular narratives which frame systems and their dynamics in different ways, promote particular goals and values, and justify particular pathways of disease response. These range from ‘outbreak narratives’ emphasising threat to global populations, to alternative but often marginalised narratives variously emphasising long-term structural, land use and environmental change, local knowledge and livelihood goals. We highlight tendencies – supported by cognitive, institutional and political pressures – for powerful actors and institutions to ‘close down’ around narratives that emphasise stability, underplaying longer term, less controllable dynamics. Arguing that governance approaches need to ‘open up’ to embrace strategies for resilience and robustness in relation to epidemics, we outline what some of the routes towards this might involve, and what the resulting governance models might look like. Key are practices and arrangements that involve flexibility, diversity, adaptation, learning and reflexivity, as well as highlighting and supporting alternative pathways within a progressive politics of sustainability.