We describe an integrated theory of olfactory systems operation that incorporates experimental findings across scales, stages, and methods of analysis into a common framework. In particular, we consider the multiple stages of olfactory signal processing as a collective system, in which each stage samples selectively from its antecedents. We propose that, following the signal conditioning operations of the nasal epithelium and glomerular-layer circuitry, the plastic external plexiform layer of the olfactory bulb effects a process of category learning—the basis for extracting meaningful, quasi-discrete odor representations from the metric space of undifferentiated olfactory quality. Moreover, this early categorization process also resolves the foundational problem of how odors of interest can be recognized in the presence of strong competitive interference from simultaneously encountered background odorants. This problem is fundamentally constraining on early-stage olfactory encoding strategies and must be resolved if these strategies and their underlying mechanisms are to be understood. Multiscale general theories of olfactory systems operation are essential in order to leverage the analytical advantages of engineered approaches together with our expanding capacity to interrogate biological systems. © Copyright © 2020 Cleland and Borthakur.