The Food and Drug Administration (FDA) serves as the primary regulatory gatekeeper for health products entering the American market. While not always ideal, for most of the twentieth century, the statutory rubric of the Federal Food, Drug, and Cosmetic Act (FDCA), the main statutory foundation for FDA's authority, has worked quite well. In 1962, FDA gained authority to regulate not just safety, but efficacy, of drugs. In the decades following, with limited congressional assistance, FDA has stretched and twisted its authority to deal with new technology. In 1976, that authority was extended to devices. In the latter decades of the century, FDA's authority has been applied to regulate technologies such as cellular products, software, and genomic testing. FDA has approved thousands of products and for most of the twentieth century, despite periodic complaints about the length of time to approval, most stakeholders have been generally satisfied with the overall approval process, if not specific decisions within that process. But this model is applicable to the production of products for widespread use in the general population based on twentieth-century notions of disease and therapy. With limited exceptions, an approved product is designed to be used by anyone affected by a specified condition, often many hundreds of thousands of people. In 2004, the Vioxx experience revealed some of the holes in that rubric because only after approval did it become clear that a segment of the population using the drug suffered cardiovascular effects.'But that problem, which exposed potential for existing but limited human variability in drug response in a drug that was mostly safe and effective for a large population, is fairly resolvable through better postmarketing surveillance. 2 It is less clear that the overarching structure of the FDCA can effectively deal with one of the most promising innovations of the twenty-first century-personalized medicine-which not only exposes human variability, but embraces it. Current attempts to harmonize the demands of personalized medicine with the requirements of the FDCA involve the inclusion ofpharmacogenomic information in product labeling and the development and