This document provides the motivations and a brief introduction to the Special Issue entitled “Advanced Control Design and Fault Diagnosis”, which aims at presenting several solutions to the advanced control design and fault diagnosis systems. These methodologies can be considered in the general framework of advanced control, fault diagnosis and fault tolerant control systems, which are also able to improve the safety of the system under monitoring. The focuses of the current research in this field addressed in this Special Issue are also presented with emphasis on the practical application to simulated and realistic examples, which should provide an overall picture of current and future developments in this area. The works of this Special Issue represent suitably extended contributions selected by the proponents from the ACD2019—the 15th European Workshop on Advanced Control and Diagnosis, which was organised in Bologna, Italy on November 21st–22nd.