The chapter presents learning regions, understood as regional development coalitions, as a strategy for economic development in less developed regions. This follows a long tradition of regional innovation policy making, where this bottom-up and inclusive approach has been applied to promote learning-based processes of innovation and change. The first example was the Regional Innovation Strategies actions of the EU Commission in the late 1990s focusing on supporting innovation in less developed regions. Today, learning regions, the chapter argues, can be applied to design and implement Smart Specialization Strategies, which is the present EU regional innovation policy, in less developed regions of Europe. The learning region strategy of building broad regional development coalitions would be a way of activating the entrepreneurial discovery process, a cornerstone in smart specialization, in less-developed regions by mobilizing people with an entrepreneurial mindset from all sectors of a community to start a process of economic development.