Identifying biologic and behavioural causes of disease has been one of the central concerns of epidemiology for the past half century. This has led to the development of increasingly sophisticated conceptual and analytic approaches focused on the isolation of single causes of disease states. However, the growing recognition that (a) factors at multiple levels, including biologic, behavioural, and group levels may influence health and disease, and (b) that the interrelation among these factors often includes dynamic feedback and changes over time challenges this dominant epidemiologic paradigm. Using examples we will discuss how this deterministic paradigm has led us down a narrow path that challenges our capacity to meaningfully understand the complex causes of health states. Once we begin ‘thinking in systems’ we inevitably arrive at a broader public health conceptualization of the causes of health states. This has important implications both for the science as well as for a public health policy approach that aims to improve the health of populations.