Cancer, as an ultimate result of exposure to chemicals, has been described for at least 200 years and it has probably existed as long as man. When the span of human life was short due to epidemic disease, war, and famine, cancer was not a major concern. However, as most causes of early death have been conquered, cancer emerges as one of the most common causes of death in late life. Evaluation of the extent to which exposure to, or ingestion of, chemicals causes cancer is not the purpose of this book. Rather, we will examine what is known of the chemical and biochemical reactions of different classes of carcinogenic chemicals, or their metabolites, with cellular components. This study will focus primarily on nucleic acids, and most specifically on the mechanism of the initiation stage of carcinogenesis. Initiation in this context is the term for the covalent binding of a reactive group to a nucleotide in an informational macromolecule. For this reason, reaction with other cellular components such as proteins, lipids, and polysaccharides is not included.