Outlining the scope for process systems engineering studies in proton exchange membrane fuel cells (PEMFC), this chapter presents a review of opportunities. Proton exchange membrane fuel cells PEMFCs are currently in an advanced state of development with promising applications for portable power and power generation. In spite of this, even today, there are several critical issues that researchers are trying to address and resolve. This chapter highlights some of the important technological advancements made in the areas of (i) flow field design and (ii) water and thermal management. A review of the state-of-art in engineering and design in each of these areas are also summarized in the chapter. At the same time, it also highlight the areas where opportunities exist for process systems engineering activities such as, modeling and simulation, optimization, control, diagnostics, and fault-tolerant control. The focus of the research work being discussed in this article is the systems engineering of PEMFC with the help of both detailed models and reduced order models.