Computational simulations of layered double hydroxides (LDHs), based on relatively simple models and simulation procedures (classically based force-field calculations), are shown to be an effective technique for rationalizing the orientation of guest species. It is demonstrated that the simulations yield values for the gallery heights that agree well with those observed experimentally and that intercalated water plays an important role. LDHs are of interest for applications in catalysis, medicine, molecular sieving, electrochemistry, and oil-field exploration.