In this work, two mathematical models of different level of complexity are proposed as tools for design and optimization of the operation of industrial-scale gas separation membrane reactors. First, a simple model is developed, which provides quick predictions and preliminary performance values for the design of the full-scale membrane reactor. This model is a useful tool for process design studies and membrane reactor pre-design. In the second approach, the reactor operation is simulated by detailed membrane reactor modelling, using computational fluid dynamics techniques and taking into account transfer processes that take place in membrane reactors. Results from the application of both models to the design of a membrane reactor operating with highly selective membranes, as used in an Integrated Gasification Combined Cycle plant for better energy efficiency and control of CO2 emissions, are presented and discussed. On the basis of these results, a better insight can be achieved into the factors determining the membrane reactor performance.