This paper considers the challenges entailed in applying the principles and methods of public participation to national and international policy processes. It draws on evidence from the field of biotechnology policy and biosafety regulation in Brazil, Canada, China, Denmark, Estonia, Ethiopia, India, Kenya, Malaysia, Mexico, Namibia, New Zealand, Norway, the United Kingdom, the United States and Zimbabwe. The paper makes a distinction between the regulatory-scientific concept of “biosafety” and the more encompassing and socially-defined politics of “biotechnology”. “Biosafety”, developed largely at the international level, frames the regulatory issues relating to genetically modified organisms (GMOs) within narrow and technically-defined boundaries. As a consequence of the drive to harmonise and normalise biosafety regulation internationally, it has confronted the more diverse, unruly and contested politics of biotechnology at national and local levels. The way in which participation occurs in practice is shaped and constrained by the interplay of the politics of “biosafety” and international harmonisation on one hand, and the more inclusive politics of biotechnology on the other, in particular national contexts. The experiences of the 16 countries are discussed along three dimensions: the influence of the European Union’s moratorium on GMOs; their domestic contexts (including ecological, socio-economic and political-cultural factors, as well as international aid, trade and investment relationships); and their domestic capacity in biotechnology research and development. While there are positive examples to be found in the experiences of different countries, generally there is an unsatisfactory compromise between the obligation to promote public participation and the need to conform to international standards. Often, lip service is paid to participation without providing the substance. More seriously, even when governments have the will to include the public in decision making, they may lack the capacity to do so effectively, or to stand by the concerns of their publics in the face of opposition from powerful foreign countries.