An assessment of changing care and prevention needs in the framework of global public health should not be just a technical exercise of 'standard' demographic and epidemiological analysis; rather, it should also involve a reflection on the conditions of the production of such knowledge. In this article, we start by outlining some key dimensions of change in demographic and epidemiological patterns as well as their drivers; second, we address in more depth the question of whether current scientific practice is generating all the questions needed to improve global health in the coming years, and define potentially effective strategies for positive change. Significant demographic changes (i.e., reductions in earlier mortality and fertility; ageing and urbanisation) are leading to the emergence of chronic diseases in the Global South, as well, although patterns are very diverse, and early mortality and disability will still remain high for a few decades in certain areas. Such inequality in health patterns seems to parallel globalisation processes, and results from the effects of social and structural determinants. To better understand those relationships, we must improve our thinking about causality as well as our standard views of what constitutes 'good evidence'.