As process optimization becomes an established and mature technology for process simulation, analysis and operation, it becomes important to consider larger and more creative problem formulations and applications, as well as the development of efficient algorithms to tackle them. Here, some novel process optimization applications are briefly reviewed in the following areas of process design and analysis:• treatment of constrained and nonsmooth simulation problems, particularly in phase equilibrium • synthesis of chemical reactor networks through the application of targeting strategies • more efficient strategies for process optimization and postoptimality analysis • treatment of uncertainty through multiperiod optimization problems • the role of automatic differentiation tools in process optimization An outline of the concepts behind each of these topics will be presented and process examples are briefly described in order to demonstrate the effectiveness of these optimization-based applications.