Metal-organic frameworks (MOFs) are a new class of nanoporous materials with potential applications in adsorption separations, catalysis, and gas storage. Several reports have suggested their use for hydrogen storage as part of a hydrogen economy, but most experimental studies to date have only reported interesting uptake at cryogenic temperatures. Storing substantial amounts of hydrogen by physisorption at room temperature and reasonable pressures is a very challenging goal. Molecular simulations can play an important role in improving our understanding of hydrogen storage by physisorption and our general understanding of adsorption in MOFs. In our previous work, we performed grand canonical Monte Carlo (GCMC) simulations of hydrogen in a series of 10 isoreticular metal-organic frameworks (IRMOFs) at 77 K over a wide range of pressures. The results showed acceptable agreement with the limited experimental results from the literature. The results revealed the existence of three adsorption regimes: at low pressure (i.e. low loading), hydrogen uptake correlates with the heat of adsorption; at intermediate pressure, uptake correlates with the surface area; and at the highest pressures, uptake correlates with the free volume. Some MOFs have incredibly high surface areas (up to ~4000 m2/g) and high free volumes on a gravimetric or volumetric basis. However the heat of adsorption is low, so adsorption at room temperature is well below targets for practical hydrogen storage. We are, therefore, evaluating strategies for improving the heat of adsorption. First, we perform room-temperature GCMC simulations in which the adsorbate/MOF interaction is artificially increased. This makes it possible to establish a target for the heat of adsorption (determined by the adsorbate/MOF interaction) that will give acceptable hydrogen uptake at practical temperatures and pressures. New mixed-ligand MOFs are also evaluated through GCMC simulations. Some of these new MOFs allow for ligand reduction and the introduction of counter-balancing cations. The increased polarizability of the reduced ligands and the electric fields generated by the cations are expected to improve the heat of adsorption. This effect is being tested using quantum chemical calculations of hydrogen binding to reduced ligand/cation complexes.