Concern that chemicals in the environment can disrupt the endocrine systems of humans and ecological species (fish, frogs, birds) has driven the development of bioassays to test for endocrine activity. In the last decade, there has been increased focus on in vitro and high-throughput screening (HTS) assays and in silico models that allow the rapid evaluation of hundreds to thousands of compounds. We review efforts at the US EPA and the National Toxicology Program to develop assays and models to predict estrogen, androgen and steroidogenesis activity. These approaches include in vitro HTS assays, computational models that link the results of multiple assays and reduce the impact of assay artifacts and noise, and structure-based QSAR models. These approaches have been shown to be robust enough to move from research to application in regulatory risk assessment. Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.