Social determinants of health have come to greater prominence through the recent work of the WHO Commission on the Social Determinants of Health, and the Marmot Review of Health Inequalities in England. These reports also have significant implications for promotion of mental health in developed countries. In particular they reflect a growing research interest in the view that certain adverse social conditions may detrimentally affect mental or physical health by acting as chronic stressors. However, although the case for chronic arousal of stress systems as a risk factor for mental health is empirically well-founded, questions remain about how and why psychological exposure to certain kinds of proximal social conditions might contribute to such arousal. In this paper we argue that combining evidence and ideas from a number of disciplines, including public health research and psychiatry, presents an opportunity to understand the relationship better, and so inform complementary strategies in treatment, prevention and health promotion.