In this final part, we discuss fault diagnosis methods that are based on historic process knowledge. We also compare and evaluate the various methodologies reviewed in this series in terms of the set of desirable characteristics we proposed in Part I. This comparative study reveals the relative strengths and weaknesses of the different approaches. One realizes that no single method has all the desirable features one would like a diagnostic system to possess. It is our view that some of these methods can complement one another resulting in better diagnostic systems. Integrating these complementary features is one way to develop hybrid systems that could overcome the limitations of individual solution strategies. The important role of fault diagnosis in the broader context of process operations is also outlined. We also discuss the technical challenges in research and development that need to be addressed for the successful design and implementation of practical intelligent supervisory control systems for the process industries. © 2002 Published by Elsevier Science Ltd.