The science of toxicology has served society well in protecting public health and the environment. Governments, the industrial sector, and the public have relied on toxicology as the foundation to assess risks to both human and ecological populations from environmental factors, including chemicals, biologic agents, physical agents, and other stressors. To maintain its prominence, the science and practice of toxicology will need to embrace the revolution underway in biology. Systems biology and biotechnologies derived from sequencing of the human genome, referred to as "genomics," have created exciting possibilities for application to human health and environmental risk assessment. Yet this rapid advance of science and technology can be overshadowed by inconsistency in study design and sampling strategies; by the lack of quantitative or qualitative correlations of exposure, dose, or adverse effects; and by the lack of bioinformatics tools and analytical methods necessary to manage the volume of research findings. These limitations may render results uninterpretable and difficult, if not impossible, to use in risk assessment. Recommendations will be discussed to improve integrating systems biology and genomics into risk assessment so that the inherent promise of these new approaches can be realized.