The science of risk assessment revolves broadly around hazard identification (toxicity) and exposure assessment information. While exposure to environmental hazards most often occurs with complex chemical mixtures, the majority of existing toxicity data is for single compounds or simple mixtures, thus presenting problems to the risk assessor. Several approaches to assess mixtures have been developed (e.g. Hazard Index; Target-organ Toxicity Dose; Weight-of Evidence; Toxic Equivalence), each of which have their limitations, primarily with respect to the prediction of potentially unforeseen interactions between the mixture constituents which may affect their resultant toxic outcome. Recent advances in disciplines such as genomics, proteomics, metabonomics and physiologically-based pharmacokinetic modeling should assist in the hazard assessment of complex chemical mixtures. However, the process of regulatory assessment of these types of exposures will remain both complex and difficult.