Using the concept of vulnerable populations, we examine how disparities in health may be exacerbated by population-approach interventions. We show, from an etiologic perspective, how life-course epidemiology, the concentration of risk factors, and the concept of fundamental causes of diseases may explain the differential capacity, throughout the risk-exposure distribution, to transform resources provided through population-approach interventions into health. From an intervention perspective, we argue that population-approach interventions may be compromised by inconsistencies between the social and cultural assumptions of public health practitioners and targeted groups. We propose some intervention principles to mitigate the health disparities associated with population-approach interventions.