The notion that income inequality exerts an influence on health status (over and above the long-known effects of individual or household income) has received a great deal of attention in social epidemiology, medical sociology, and economics in the past twenty years. And although a clear consensus on the hypothesis has yet to emerge, a new wave of empirical studies has strengthened the case for seeing income inequality as a social determinant of health. This paper examines the current trajectory of the income inequality – health literature, and explores two issues that will be critical to its development in the coming years: (1) the need to re-examine the epistemological grounding of this research area, with a corresponding shift towards blurring the division between positivism and critical realism, and (2) the value of re-considering the geo-political ‘frame’ of studies in this field, with a move towards a truly global analysis of the health effects of income inequality.