This article explores the history of regions, centralism and regionalism in Italy ‒ a highly controversial political field of state reorganization over 150 years. Focusing on the status of regions within Italy’s political power structure and the development of the multi-level governance system, the article draws a line from the foundation of the Italian national state in 1860/61 to the immediate present. It examines political aspirations for decentralized structures and changing perceptions of how to reorganize the state to create efficient structures in different eras as well as power shifts between the different political levels. The article shows that Italian politics oscillated between centralism and regionalism. Reforms took place against the backdrop of different political systems and public debates in a heterogonous country. Since the mid-nineteenth century, the Italian public discussed a federal structure and decentralization. Altogether, reforms were implemented inconsistently, slowly and gradually: The long-term analysis highlights the complexity of constitutional reforms within the background of a set of actor’s including regionalist movements, political parties and traditionalist and regionalist sentiments. What we observe is a highly ideological debate on decentralization followed by reservations and resistances across the state. The article concludes that looking at today’s Italian politics, attempts for recentralization are gaining ground again. However, the article identifies several dimensions of state transformation. Notions of efficiency and legitimacy have to be taken in account just as much as regional self-interests, diverse structures inherited from the past and the asymmetry of the Italian federalist system. The author stresses the need for a more holistic approach, for a detailed examination of the relationship between those dimensions together with a shift in global power structures. The contribution thus proceeds to develop a multifaceted framework in order to facilitate further research, to understand more fully the shift of power within the Italian multi-level system.