In the aftermath of the BSE crisis (mad cow disease), the European Union (EU) resorted to the setting up an EU agency in order to be better able to tackle complex and uncertain policy problems in the field of food safety. Overall, we see an increasing reliance on agencies as providers of expert advice in case of complex policy problems, yet we know relatively little about how agencies actually act in such situations. This paper analyses the way in which the EU tackles complex policy problems via the case study of the handling of the H1N1 pandemic in the European Centre for Disease Prevention and Control (ECDC). By outlining how complex policy problems are analysed in different disciplines (complex policy problems as ‘wicked problems’, ‘risks’, and ‘crises’), we analyse how ECDC handled uncertainty during the H1N1 pandemic crisis in 2009. This analysis demonstrates that learning from the BSE crisis took place and that ECDC is very explicit in acknowledging uncertainty; it refrains from providing ‘false certainties’ and highlights the ‘known unknowns’.