This article examines some of the open issues that should be addressed regarding physiological modeling and information processing to make them central in the future. Coupling model and data through multiple scales and organization levels, multimodal signal and image processing represents a major step in this respect. The capability to bridge physiological models and homogeneous data leads to identification of the systems at hand. However, it is not enough to address a given property of any living system because it has multiple biophysical expressions, all consisting of interdependent or coordinated functions. Structure and function types cannot be easily separated, they are both distinct (large variety and heterogeneity, highly variable behaviors) and connected (with constraints, redundancies, and strong dependency). These issues are examined here together with some more practical considerations.