Over the past 3 decades minipigs have moved from being an obscure alternative to dogs and nonhuman primates to being a standard animal model in regulatory toxicity studies. This article covers the use of minipigs as a model in the context of nonclinical drug safety and provides an overview of the minipig’s developmental history and relates minipigs to other animal species commonly used in toxicology; and the minipig’s translational power is supported by 43 case studies of marketed drug products covered. Special focus is given to criteria for selecting minipigs in nonclinical programs supporting the development of new medicines; the use of swine in the assessment of food additives, agrochemicals, and pesticides; as well as a regulatory perspective on the use of minipigs in Food and Drug Administration (FDA)-regulated products. This article presents the main points conveyed at a symposium held at the 2010 American College of Toxicology meeting in Baltimore, Maryland.