The US FDA’s mission is to ensure that safe and effective drugs are approved for use by American consumers. Among the many factors that the FDA examines to ensure that drug products are safe and effective is the effect of food on the bioavailability of the active drug from the drug product. Thus, the FDA asks applicants seeking marketing approval of new or generic drug products to conduct human pharmacokinetic studies examining the effects of food on drug absorption and bioavailability. The objectives of this chapter are to (1) describe several mechanisms by which food affects drug bioavailability; (2) present examples from FDA-approved drug product labeling to show how food effects are considered in optimizing therapy; (3) distinguish between food effects on drug substance versus drug product; and (4) explain the role of food-effect studies in new and generic drug development.