This paper presents various aspects of modeling, simulation, design, and optimization of membrane-based gas separation systems. A model for counter- and crosscurrent membrane modules and an efficient numerical solution procedure based on orthogonal collocation to solve the differential model equations have been developed. The model handles multicomponent mixtures and considers effects of pressure drop and energy balance. The model and solution procedure are combined in a versatile unit which can be conveniently used in a process simulator. The solution procedure allows analytical calculation of sensitivities. The membrane module has been implemented and tested in an external process simulator, OPTISIM, which is based on the equation-oriented approach. The cost optimization features of OPTISIM have then been used to investigate hybrid schemes for CO pretreatment of steam reformer gas:The traditional cold box has been modified with a membrane unit and the results of the cost optimization calculations are presented.