In this chapter, we analyse the rationale of regional policies, discuss the evidence, and highlight some methodological problems. In doing so, we also take a closer look at policy consequences that follow from or can be linked to the models discussed throughout the book. In some of our thought-experiments, we take the models of the book literally and ask, what would be the lessons for policy makers? When we discuss actual cluster/regional policy thinking, but also when we discuss hypothetical policies by sticking as closely as possible to our models, there are always three main elements to take into account. First, whether it is a people- or place-based policy (or a mix of these two). Second, to go beyond the observation that a policy can change spatial economic outcomes by showing that a policy is somehow welfare improving. Third, to take into consideration the important macro/micro distinction in terms of regional policy effectiveness: a ‘good’ regional policy at the city or regional level does not necessarily imply that it is also beneficial for the economy as whole. The main message of the chapter is that regional policies should be handled with care.