The understanding of variability in response is critical in accounting for interindividual variability in susceptibility and, hence, risk, if the regulatory community and others are expected to characterize human health risks associated with exposure to chemicals. Models for incorporating measures of response variability in the risk assessment process are critically reviewed and illustrated with published data. This authoritative work indicates that, in the case of certain chemicals and in the context of certain specific toxic effects, we have considerable ability to predictively and quantitatively characterize human variability, but, in the majority of cases, our ability to do so is limited. If we improve both quantity and quality of information available on response variability and increase our understanding of target tissue dosimetry, we should be better able to account for variability in human susceptibility to the toxic effects of chemicals.