The biochemical facets of toxicology have always had a major role in providing insight into mechanisms. Some of the history of the development of this area is summarized, including metabolism, enzymology, and the chemistry of reactive intermediates. Knowledge in these fields has had a major impact in the areas of drug metabolism and safety assessment, which are both critical steps in the development of pharmaceuticals and the rational use of commodity chemicals. The science of toxicology has developed considerably with input from other disciplines and today is poised to emerge as a predictive science with even more dramatic impact. The challenges ahead are considerable but there is renewed excitement in the potential of the field. As in the past, further advances in the field of toxicology will require the input of knowledge from many disciplines.