This book introduces the Ontology of Physics for Biology (OPB), a computable knowledge resource for representing, annotating, and reasoning about multiscale, multidomain physiological systems. It links qualitative reasoning to quantitative analysis of biophysical processes in health and disease. The authors’ work is presented in the context of two major public health problems, diabetes and hypertension, to illustrate the depth and rigor of their semantic representations for logical inference and quantitative analysis. OPB provides a computable representation of classical physics and engineering system dynamics that serve as the basis for scientific understanding of biophysical entities, processes, and their functional relationships. The formal semantic definitions in the OPB are useful for annotating, abstracting, and reusing the biophysical content of available physics-based models and for analyses of multiscale, multidomain models and data. The authors present their formalized view of physics-based biological knowledge from the perspectives of (1) biologists and biomedical investigators, (2) biophysicists and bioengineers, and (3) biomedical ontologists and informaticists. The authors’ unique approach for formally representing and organizing the scientific knowledge articulated in models of biological systems is applicable across a wide range of scientific research domains and biological scales. The book will be a useful guide for undergraduate, graduate, and professional students of bioinformatics, biomedical ontology, and biophysical modeling.