Mesoporous materials, which exhibit great potential in the control of polymorphs and delivery of poorly water-soluble drugs, have obtained considerable attention in the field of pharmaceutical science. The physical properties and release behaviors of amorphous or crystalline drugs may be affected by formulating them into mesoporous drug delivery systems. In the past few decades, an increasing amount of papers have been written about mesoporous drug delivery systems, which play a crucial role in improving the properties of drugs. Herein, mesoporous drug delivery systems are comprehensively reviewed in terms of their physicochemical characteristics, control of polymorphic forms, physical stability, in vitro performance, and in vivo performance. Moreover, the challenges and strategies of developing robust mesoporous drug delivery systems are also discussed.