Mechanistic physiological modeling is a scientific method that combines available data with scientific knowledge and engineering approaches to facilitate better understanding of biological systems, improve decision-making, reduce risk, and increase efficiency in drug discovery and development. It is a type of quantitative systems pharmacology (QSP) approach that places drug-specific properties in the context of disease biology. This tutorial provides a broadly applicable model qualification method (MQM) to ensure that mechanistic physiological models are fit for their intended purposes.