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This paper investigates whether and in what way regional and cohesion policies defined at the European level provide resources for alleviating the impact of company restructuring and processes of large-scale structural adjustment on workers and territories. It also looks into the capacity of regional and local authorities to anticipate such developments. Going back to the origin of EU regional policy, we find that it was precisely designed for the purpose of accompanying the completion of the single European market and fostering adaptation to externally-driven change as competition became fiercer. Since then, EU structural funds have played a double role. On the one hand, they have functioned as an embryo of a European policy for economic development, relying on public expenditure representing a sizable share of the EU budget. On the other hand, they have led to implementing a new governance system aiming to integrate a large number of actors in the definition of developmental strategies and reinforcing the regional level. The paper acknowledges the great variety of situations across regions, and it draws some lessons from several empirical cases. It concludes by identifying a number of necessary conditions to be fulfilled for an active utilization of structural funds, in particular when facing large-scale restructuring.