There is a growing literature on the use of science to inform decisions on the environmental, health and safety implications of nanotechnology, but little has been published by those who make such decisions. Here, as officials of the US Environmental Protection Agency, the European Commission and the Organisation for Economic Co-operation and Development, we discuss the types of decision facing government regulators, the new considerations nanotechnology brings to decision-making, the role of science in informing decisions, how regulators cooperate internationally on policy issues, and the challenges that lie ahead.