In this paper the authors argue that neighborhoods are highly relevant for the types of issues at the heart of regional science. First, residential and economic activity takes place in particular locations, and particular neighborhoods. Many attributes of those neighborhood environments matter for this activity, from the physical amenities, to the quality of the public and private services received. Second, those neighborhoods vary in their placement in the larger region and this broader arrangement of neighborhoods is particularly important for location choices, commuting behavior and travel patterns. Third, sorting across these neighborhoods by race and income may well matter for educational and labor market outcomes, important components of a region's overall economic activity. For each of these areas we suggest a series of unanswered questions that would benefit from more attention. Focused on neighborhood characteristics themselves, there are important gaps in our understanding of how neighborhoods change - the causes and the consequences. In terms of the overall pattern of neighborhoods and resulting commuting patterns, this connects directly to current concerns about environmental sustainability and there is much need for research relevant to policy makers. And in terms of segregation and sorting across neighborhoods, work is needed on better spatial measures. In addition, housing market causes and consequences for local economic activity are under researched. The authors expand on each of these, finishing with some suggestions on how newly available data, with improved spatial identifiers, may enable regional scientists to answer some of these research questions.