The proposed panel contains a selection of the contributions scheduled for a journal special issue on challengers and challenges to federalism in Europe and beyond. It is interesting to note that when considering the issue of the resilience of the EU, systematic comparisons between the EU and federations are surprisingly rare. Whereas the most frequent comparison is between the EU and the US, only a few studies compare several federal states and the EU with the help of an explicit comparative design. This is unfortunate because federations seem to experience similar problems and evolutionary patterns to that of the EU, and thus invite comparison, particularly as the EU increasingly moves into core state powers. The panel seeks to establish what we may learn from examining the EU from a federal perspective. In doing so we need to consider how federalism is changing in today’s interdependent world. The EU represents an effort at reconfiguring state sovereignty (and its own federal and quasi-federal member states); thus its experience may give added impetus to the need to reconsider federalism in today’s world. The panel accordingly seeks to discern lessons from comparing the EU and federal systems, as part of a broader effort at establishing the prospects for federalism in today’s interdependent world, by drawing mainly on the EU experience.