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The five EU-centered challenges alluded to in the title of this paper include 1) the rise of populist politics in Europe; 2) the difficulties posed by a more 'assertive' Russia; 3) the conflicts, instability and socioeconomic deprivation affecting parts of North Africa and the Middle East; 4) the changing nature of America's role in the world and its ties with the EU; and 5) the growth of multipolarity.