In this chapter, Sunderland and Wagner examine society’s historical relationship with chemical toxicants and how exposure to such toxicants has reached a global scale since the first Earth Day. This increase in exposure is due, in part, to population growth, which has caused an increased reliance on chemicals, both natural and synthetic. For the vast majority of these chemicals, we have only a limited understanding of how they will behave once released into the environment. They turn their attention to a fundamental problem with synthetic chemicals – their persistence in nature, which means that they do not readily break down following release into air, water or soils. As a result, the blood of nearly every mammal on the planet now contains a cocktail of toxicants. Sunderland and Wagner further examine how public awareness of the health risks associated with exposure to contaminants is only prevalent when the health risks are visible or result in death. After delving into what we have learnt over the past several decades through exposures to a wider range of anthropogenic chemicals, they turn their attention to issues in regulating the production and release of toxicants into the environment, emphasizing especially the tendency to adopt reactionary rather than proactive approaches. Advocacy and public outrage still remain the most effective method for enacting changes in chemical use and releases. However, addressing the global chemical experiment requires a new kind of thinking about environmental issues – one that does not isolate chemical engineers from environmental toxicologists and health scientists, and one which increasingly uses screening tools prior to widespread use of chemicals.