Considerable advances have been made over the past century in the understanding of the chemical hazards in food and ways for assessing and managing these risks. At the turn of the 20th century, many Americans were exposed to foods adulterated with toxic compounds. In the 1920s the increasing use of insecticides led to concerns of chronic ingestion of heavy metals such as lead and arsenic from residues remaining on crops. By the 1930s, a variety of agrochemicals were commonly used, and food additives were becoming common in processed foods. During the 1940s and 1950s advances were made in toxicology, and more systematic approaches were adopted for evaluating the safety of chemical contaminants in food. Modern gas chromatography and liquid chromatography, both invented in the 1950s and 1960s, were responsible for progress in detecting, quantifying, and assessing the risk of food contaminants and adulterants. In recent decades, chemical food safety issues that have been the center of media attention include the presence of natural toxins, processing-produced toxins (e.g., acrylamide, heterocyclic aromatic amines, and furan), food allergens, heavy metals (e.g., lead, arsenic, mercury, cadmium), industrial chemicals (e.g., benzene, perchlorate), contaminants from packaging materials, and unconventional contaminants (melamine) in food and feed. Due to the global nature of the food supply and advances in analytical capabilities, chemical contaminants will continue to be an area of concern for regulatory agencies, the food industry, and consumers in the future.