In 2005, in recognition of the role of social factors in increasing health inequities, the World Health Organisation established the Commission on the Social Determinants of Health. South Africa is among the most unequal societies in the world. It faces serious public health challenges, including an elevated burden of chronic disease, and high levels of violence. This paper presents data from a cross-sectional study of socio-economic and health status conducted in five Johannesburg housing settlements in 2006. The findings paint a picture of health inequities across and within the study sites, and socio-environmental conditions that undermine the prospects of protecting and promoting health. The authors suggest the need for a new approach to public health in areas of urban impoverishment in Johannesburg and elsewhere.