Silica-based nanoparticles have recently raised a great deal of attention as possible drug carriers. Such an interest is driven by the possibility to control their size, the chemical composition and the porous structure as well as to easily modify their surface with a wide range of biologically-relevant functionalities, favoring colloidal stability, long-time blood circulation and even specific targeting. Drug loading can be performed during particle formation but, at this time, the most popular method relies on the impregnation of pre-formed mesoporous colloids. Strategies to control drug delivery via bio-responsive pore capping are also developed. However, despite an increasing number of in vitro and in vivo studies related to the interaction of silica particles with cells and animals, their biocompatibility is still an issue, especially if applications in intracellular drug delivery are foreseen.