Scientific discoveries in the environmental health sciences emerging over the past 15 years have increasingly challenged the safety of a variety chemicals that have become commonplace in consumer products as well as in the environment. Four core discoveries underpin this challenge: (1) concentrations once thought too low to be harmful are now known to have biological activity; (2) mixtures of compounds can cause significant harm even when each component of the mixture is at a level too low to cause an effect; (3) exposures early in life can reprogram development, leading to diseases and disabilities that may not be apparent at birth; and (4) the use of high dose testing in regulatory toxicology is incapable of detecting these effects. Because of their widespread use, human exposure to these chemicals is ubiquitous. For some compounds, levels detectable in humans are within the range of concentrations that have been shown to cause adverse effects in laboratory experiments with animals and cells. The research findings provide plausible but uncertain evidence linking exposures to a range of human health conditions, including cancers, reproductive, neurodevelopmental and immune system damage, as well as type 2 diabetes, obesity and heart disease. Developing new materials through green chemistry may avert some portion of the burden of these diseases.