This article employs Ulrich Beck's (1992, 1999) formulation of incalculable risk to analyze chronic disease in contemporary western society and the resultant social transformations across multiple levels of scale. Specifically, we explore the social structures in which management of contemporary health risks is embedded, as well as how the social psychological implications of risk incalculability affect individuals. These micro-level phenomena in turn feed back into cultural transformations in health knowledge and health-care institutions. We discuss the rising significance of health lifestyles following the epidemiological transition as a starting point from which to analyze the incalculable nature of chronic disease risk, paying special attention to the ways that fracturing medical knowledge underlies the development of a variety of often opposing lifestyle practices. Medicine has responded to these developments by institutionalizing a diversity of alternative health-care models, and we organize these complex processes around macro- and micro-levels of scale using Beck's theory of risk in contemporary society as a starting place. © 2011 Macmillan Publishers Ltd.