Recognizing natural history collections as dynamic scientific tools that enable unique forms of comparative analysis, theorizing, and questioning offers a new perspective on the history of the life sciences in the twentieth century that emphasizes the important role that collections played in the transformation of biology. To build an understanding of “collections-based research,” this paper focuses on the career of Alden Holmes Miller, who led the Museum of Vertebrate Zoology at the University of California, Berkeley through significant institutional, disciplinary, and technological changes (1940–1965). This paper examines how Miller’s efforts as researcher, administrator, and teacher enabled him to foster collections-based research. Miller’s own research into speciation and reproductive physiology are examples of collectionsbased work, incorporating concepts, theories, practices, and tools from the laboratory, museum, and field.