In recent years Italy has moved towards greater devolution of regulatory powers at regional level, in a European context where this dimension becomes increasingly important. This review analyses first the institutional set-up for multi-level regulation, the specifics of power sharing between the State and the regions, as well as the horizontal and vertical co-ordination mechanisms in place in the country, before turning to the use of policy instruments and regulatory tools in four Italian regions: Veneto, Calabria, Campania and Tuscany.