Systems biology research is currently dominated by integrative, multidisciplinary approaches. Although important, these strategies lack an overarching systems perspective such as those used in engineering. We describe here the Axiomatic Design approach to system analysis and illustrate its utility in the study of biological systems. Axiomatic Design relates functions at all levels to the behavior of biological molecules and uses a Design Matrix to understand these relationships. Such an analysis reveals that robustness in many biological systems is achieved through the maintenance of functional independence of numerous subsystems. When the interlinking (coupling) of systems is required, biological systems impose a functional period in order to maximize successful operation of the system. Ultimately, the application of Axiomatic Design methods to the study of biological systems will aid in handling cross-scale models, identifying control points, and predicting system-wide effects of pharmacological agents.