Toward the end of his life, a shift occurred in Walter Isard’s thinking about how graduate study in regional science should proceed. This shift and its implications for the discipline itself have led me to problematize Walter’s sense of the scientific in regional science. In this article, I offer a highly stylized characterization of what Walter thought regional science should be about at various points of his life and relate the evolution of his thinking to recent work in the philosophy of science. I shall argue that Walter’s view of what made regional science a science did not change much, nor did his view of what in general regional scientists needed to study. I shall also argue that his view of what constituted adequate scholarship did change considerably, as did his views of what regional science should encompass in the way of theory and methods and what future progress in the field will entail.