The Middle East and North Africa (MENA) region has been beset by a series of external interventions, regional crises and local conflicts – most recently precipitated by the Arab uprisings – that have led to major uncertainties and changes in the existing order. The aim of this paper – which launches Work Package 5 within the MENARA project – is to provide a general framework within which to understand and contextualize the transformations in regional dynamics, particularly since the uprisings. It is divided into four parts, focusing on the major regional actors (state and non-state); regional conflicts (Arab–Israeli, Syrian, Moroccan–Algerian and Sahel); themes (i.e. refugees and illegal trafficking); and key regional cooperation platforms (i.e. the Arab League, the Gulf Cooperation Council, the Arab Maghreb Union and the African Union). By introducing the basic background literature, approaches and research questions, this paper, in turn, paves the way for more in-depth and focused research papers within the MENARA project.