Aqueous solubility of an active pharmaceutical ingredient is an important consideration to ensure successful drug development. Mesoporous materials have been investigated as an amorphous drug delivery system owing to their nanosized capillaries and large surface areas. The complex interactions of crystalline compounds with mesoporous media and their implication in drug delivery are not well understood. Molecules interacting with porous media behave very differently than those in bulk phase. Their altered dynamics and thermodynamics play an important role in the properties and product performance of the amorphous system. In this review, application of mesoporous silicon dioxide and silicates in drug amorphization is the main focus. First, as background, the nature of gas-porous media interactions is summarized. The synthesis of various types of mesoporous silica, which are used by many investigators in this field, is described. Second, the behavior of molecules confined in mesopores is compared with those in bulk, crystalline phase. The molecular dynamics of compounds due to confinement, analyzed using various techniques, and their consequences in drug delivery are discussed. Finally, the preparation and performance of drug delivery systems using mesoporous silica are examined.