The first consumer protections for medical products were created in the new U.S. Food and Drug Administration (FDA) and the Public Health Service in 1906. In this chapter, we first discuss the regulation of diagnostic devices. Next, we present and discuss the five fundamental elements of FDA regulation of medical devices: facility registration and product listing; safe use of investigational devices; premarket notification and product labeling; good manufacturing practices; and corrective and preventive actions for device failures. We compare and contrast the FDA with CLIA. Later, we discuss pharmacogenomic in vitro diagnostics. The chapter concludes with a section on the new regulatory challenges in assessing the use of pharmacogogenomic diagnostics and the use of targeted therapeutics.