The aim of physiological modeling and control is to study, model and understand biological processes, then to apply identification and control strategies on it as a system. It is a big challenge to combine individualized control therapies with physiological model-based robust control methods. This requires a combination of mathematical knowledge ( numeric-symbolic computations), control engineering ( system identification, control theory), computer engineering ( formal methods, software development and testing) and biomedical engineering ( physiological modeling. The paper discusses current challenges of this topic by three concrete examples: diabetes, tumor control and depth of anesthesia.