Molecular simulations play an increasingly important role in material science and engineering. Computer simulations are in many ways an “ideal” laboratory. Simulation of gas adsorption and separations in metal–organic frameworks (MOFs) can be challenging. MOFs consist of building blocks that can be easily modified on the computer. Because of the design-principle underlying the synthesis, it is important to understand MOFs structure–properties relationships. This chapter focuses on all the pieces that are necessary for this type of modeling. This chapter begins with an understanding of the theoretical foundation for the simulations. To understand adsorption, it is important to understand the properties of the MOFs and of the fluid, both are discussed in detail. The next section on adsorption shows that adsorption modifies fluid behavior, but that much of the properties present in the adsorbed phase originate from the fluid behavior. The dynamic aspect of modeling gas adsorption is diffusion, and discussed in the next section. The last section combines all previous topics into modeling the gas-host system as an adsorption or separation device.