Pregnancy exposure registries systematically evaluate pregnancies and outcomes exposed to a medicinal compound or device during the gestational period. Historically, such programs partner an academic institution with one or more pharmaceutical companies or are run solely by a pharmaceutical company. However, other examples abound. This article describes what a pregnancy exposure registry is, as well as selected methodological challenges they face, using real examples and applications. Birth Defects Research (Part A), 2009. © 2008 Wiley-Liss, Inc.