1. Robert L. Brent, MD, PhD, DSc* 1. 2. *Distinguished Professor of Pediatrics, Radiology, and Pathology, Anatomy, and Cell Biology; Louis and Bess Stein Professor of Pediatrics; Emeritus Chairman, Department of Pediatrics, Jefferson Medical College, Philadelphia, PA; Head, Laboratory of Clinical and Environmental Teratology, Research Department, Alfred I. DuPont Hospital for Children, Wilmington, DE. Objectives After completing this article, readers should be able to: 1. List the environmental drugs, chemicals, and physical agents that have been documented to result in congenital malformations and have reproductive effects. 2. List the requirements for a teratogenic exposure. 3. Describe the importance of dose when evaluating the risk of exposures. 4. Describe the most important advances in embryology, teratology, reproductive biology, genetics, and epidemiology in the past 50 years. When I was a medical student at the University of Rochester, I was fortunate to have James G. Wilson, an embryologist, as one of my teachers in the anatomy course. He was working on the effects of radiation on the embryo, which is how I became interested in congenital malformations. Many of the faculty members discouraged me from pursuing the study of the causes of birth defects as an academic goal, “Because we are never going to solve that problem.” In 1955, when I had completed medical school and graduate school, the scientific world did not even have the correct figure for the number of human chromosomes. Gregg had recently described the teratogenicity of rubella virus infection during pregnancy. The teratogenic risk of the folic acid antagonists was established, and there were experimental studies indicating that nutritional deficiencies could produce birth defects in animals. What have we learned and accomplished in the past 50 years? Thousands of previously unknown genetic diseases have been described, and many of their genes have been identified. The fields of prenatal intrauterine diagnoses, intervention, and treatment have been created. Metabolic and biochemical screening have become standard care for pregnant women and newborns. More than 50 teratogenic environmental drugs, chemicals, and physical agents have been described by using modern epidemiologic tools and the superb talents of clinical dysmorphologists. The basic science and clinical rules for evaluating teratogenic risks have …