Genetic factors, other exposures, individual disease states and allostatic load, psychosocial stress, and socioeconomic position all have the potential to modify the response to environmental exposures. Moreover, many of these modifiers covary with the exposure, leading to much higher risks in some subgroups. These are not theoretical concerns; rather, all these patterns have already been demonstrated in studies of the effects of lead and air pollution. However, recent regulatory impact assessments for these exposures have generally not incorporated these findings. Therefore, differential risk and vulnerability is a critically important but neglected area within risk assessment, and should be incorporated in the future.