Both formally and rhetorically, the ‘United Europe’ has been the dream of many generations. Over the ensuing decades, as integration helped underpin Europe’s post-war economic success, peace and prosperity became the mutually reinforcing, fundamental rationale for deepening and widening. Since the beginning of 1995, it embraces 15 Member States, and others are waiting to join. The Community today is no longer confined to cool and steal, nor even just the single market, but has become a genuine people’s Union. Built upon a series of treaties and embodied in a set of governing institutions, the EU represents a voluntary pooling of sovereignty among European countries. These countries have committed to a process of integration by harmonizing laws and adopting common policies on an extensive range of issues. But ‘Why does the European Union deal with some issues but not with others?’. Answering this question is crucial if we are to understand how the EU makes policies and what kind of political system the EU is. Keeping in mind that the Agenda setting in the EU takes place in two ways: ‘from above’, through high-level political institutions urging EU action, and ‘from below’, through policy experts formulating specific proposals in low-level groups and working parties. Based upon that the paper will try to examine and formulate a theoretical framework for understanding the differences between these two processes. Moreover, it shows how they may interact and become intertwined in the course of actual agenda setting processes. The utility of the approach is demonstrated in two contrasting case studies: one of EU anti-smoking policy and one of EU anti-bioterrorism policy.