In this chapter, the precautionary principle will be considered as the starting point for decision-making on chemicals in cases of scientific uncertainty. The principle will serve as the reference point for an analysis and a comparison of chemicals- policies and, in particular, of legislation for industrial chemicals in the European Union and the United States of America. In the second section, the precautionary principle will be described on a general level and operationalised with respect to chemicals management. The third section will focus on EU precautionary and chemicals policy and, in particular, on the recently adopted REACH regulation. A similar analysis will be made of US policies in the fourth section, with a focus on the Toxic Substances Control Act. In the fifth and concluding section, the results from the analyses will be compared and discussed with the aim to identify measures that could improve the management of chemicals under uncertainty.