Because disciplines and their cores and boundaries are subject to change, a periodic introspective assessment can be useful in evaluating the relevance of a changing discipline to the equally dynamic and pressing needs of society. Similar examinations of other disciplines, notably economics, have been conducted in part as a means of minimizing the risks of declining credibility, policy relevance, and societal benefit. With the Southern Regional Science Association celebrating recently its 50th meeting, and as regional science itself approaches its 60th year, this paper provides a reexamination of the core of regional science. We consider the theoretical and methodological underpinnings and current status, the various roles played by space in various representations, and the values that guide our policy advice and recommendations. While cores and boundaries of regional science cannot be unambiguously identified, particularly due to the considerable overlap with and lineage to other disciplines, we conclude that it is precisely the interdisciplinarity of regional science that distinguishes it from other social sciences, and ensures its continued relevance.