Throughout most of the twentieth century, the biomedical model dominated healthcare. However, the biomedical model had its critics, who proposed alternative models to replace it. Eventually, biomedicine became fragmented at its foundations with a variety of approaches to its nature and practice. Medicine's current response to this fragmentation is to combine these disparate approaches into a single system-systems medicine. In the present book, I examine the shift, during the postgenomics era, from the biomedical model to systems medicine vis-a-vis systems biology, as well as the challenges facing systems medicine's implementation in the twenty-first century. The main goal of the present book is to provide a disciplinary framework for examining the rise of systems medicine, especially in terms of the incorporation of systems biology into the biomedical model. To realize that goal, the following questions are addressed. What is a disciplinary framework? And, why is this framework important for understanding systems biology and medicine? Briefly, a disciplinary framework represents the relational structure among disparate disciplines that support and ground a discipline and its corpus. For traditional biology and medicine, that framework consists of various disciplines within the biological and biomedical sciences, including physiology, neuroscience, pathology, and epidemiology-to name a few. For the present purpose, systems biology within the last several decades is reshaping the disciplinary framework of the biological and biomedical sciences, which is also responsible for the emergence of systems medicine. In addition, the challenges facing systems medicine, especially its operationalization and implementation with respect to medical education and practice, as well as research, are also explored.