Nanosciences and nanotechnologies are set to transform the global industrial landscape, but the debate on how to regulate environmental, health and safety risks is lagging behind technological innovation. Current regulatory efforts are primarily focused on the national and regional level, while the international dimensions of nanotechnology governance are still poorly understood and rarely feature on the international agenda. However, with the ongoing globalization of nanosciences and the rapid expansion of international trade in nanomaterials, demand for international coordination and harmonization of regulatory approaches is set to increase. Yet, uncertainty about nanotechnology risk poses a profound dilemma for regulators and policy-makers. Uncertainty both creates demand for and stands in the way of greater international cooperation and harmonization of regulatory approaches. This article reviews the emerging debate on nanotechnology risk and regulatory approaches, investigates the current state of international cooperation and outlines the critical contribution that a global governance approach can make to the safe development of nanotechnologies.