The BP Deepwater Horizon oil spill disaster has reminded us, once again, the potential for systemic failures in complex engineered systems. But such systemic failures are not limited to the chemical and petrochemical industries alone. The 2003 Northeast electrical power blackout was a systemic failure. Financial disasters such as Enron, WorldCom, subprime derivatives market, and so on, also belong to the same class. Given the size, scope, and complexity of these modern engineered systems and their interactions, it is becoming increasingly difficult for people to anticipate, diagnose and control serious abnormal events in a timely manner. Practitioners in the process industries view this as the next major challenge in control systems research and application. There are two different, but related, components of the overall systemic risks management problem. One deals with the problem of process safety during real-time operations. The other deals with safety issues during the design and/or modifications of the plant or the processes. In this paper, I will present an overview of the challenges and the opportunities. Recent progress has promising implications on the use of intelligent systems for a variety of applications in the chemical, petrochemical, and pharmaceutical industries for inherently safer design, operator training, abnormal events management, and optimal process operations.