This review details the recent advancements in the design of mesoporous silica nanomaterials for controlled release drug, gene and neurotransmitter delivery applications. The high surface area (>900 m2/g), tunable pore diameter (2-20 nm) and uniform mesoporous structure (hexagonal channels or cubic pores) of the mesoporous silicas offer a unique advantage for loading and releasing large quantities of biomedical agents. Recent breakthroughs in controlling the particle size and shape of these materials have greatly improved the biocompatibility and the cellular uptake efficiency. The strategy of using various removable capping moieties, such as photo- or redox-responsive organic groups, inorganic nanoparticles, dendrimers and polymers, to encapsulate guest biomolecules inside the porous matrices further enables the utilization of these surface-functionalized mesoporous silica nanomaterials for stimuli-responsive controlled release in vitro and in vivo. In addition to the reviewed studies, many new and exciting applications of these novel materials will soon be realized.