Acting under uncertainty is a problem that pervades risk regulation across policy domains, from radioactive waste and climate change to vaccination and mobile phones, to take just a few examples. In the UK, nowhere has the problem of uncertainty been more evident than in the food domain, where there seem to be never ending conflicts over the safety or dangers of food additives, pesticides, plastics packaging, growth hormones and genetically modified organisms. The BSE crisis even contributed to the downfall of the Conservative government in the UK in 1997 and led to the reorganisation of food safety policy making with the establishment of a new Food Standards Agency (FSA) in 2000. The FSA set out to chart a new course for risk regulation that attempted to manage food safety risks by being more open, consumer-orientated and precautionary. The reform of the regime has had some success, but the FSA has been confronted with managing a range of uncertainties that have their origin not just in science but also in the practice of regulation itself. This chapter will examine these uncertainties and the difficulties that the FSA has experienced in addressing them.