Drug development is fraught with difficulties, and pharmaceutical technology is becoming increasingly complex. With the development of computer technology, the pharmaceutical industry is paying more and more attention to the model-informed drug development (MIDD) strategy in an attempt to solve the difficulties of drug development. MIDD is a rapidly developing field. However, how to apply modeling and simulation technology in the long-term, high investment, and high-risk work of drug development to improve research and development efficiency and avoid safety issues is a question worthy of careful study. In this regard, the attitude of regulatory authorities in the pharmaceutical industry cannot be ignored. This chapter summarizes the recent guidance principles and discussions on model application in the MIDD field by drug regulatory authorities in many countries, especially the US FDA. Overall, regulatory agencies are supportive and open to the development of MIDD, but they are still very cautious in the application of models.