Porous silicon (pSi) is a nanostructured carrier system that has received considerable attention over the past 10 years, for use in a wide variety of biomedical applications, including biosensing, biomedical imaging, tissue scaffolds and drug delivery. This interest is due to several key features of pSi, including excellentin vivobiocompatibility, the ease of surface chemistry modification and the control over its 3D porous network structure. With control of these physical parameters pSi has successfully been used for the delivery of a variety of therapeutics, ranging from small-molecule drugs to larger peptide/protein-type therapeutics. In this review, the authors provide a brief overview of pSi fabrication methods, particularly with regard to the need to passivate the highly reactive Si-Hx surface species of native pSi, typically via thermal oxidation, hydrocarbonization or hydrosilylation. This surface modification, in turn, controls both the loading and release of therapeutics. The authors will then report on specific case studies of leading examples on the use of pSi as a therapeutic-delivery system. Specifically, the first reportedin vivostudy that demonstrated the use of pSi to improve the delivery of a Biopharmaceutical Classification System Class 2 poorly soluble drug (indomethacin), by using thermally oxidized pSi, is discussed, as well as highlighting a study that determined the biodistribution of 18F-radiolabeled thermally hydrocarbonized pSi after oral dosing. The authors also report on the development of composite pSi–poly(D,L-lactide-co-glycolide) microparticles for the controlled delivery of protein therapeutics. Finally, the use of pSi in the delivery of bioactives, such as the successful use of thermally carbonized pSi to deliver Melanotan II, an unspecific agonist for the melanocortin receptors that are involved in controlling fluid uptake is discussed. With a growing body of literature reporting the successful use of pSi to deliver a range of therapeutics, we are entering what may be a golden age for this drug-delivery system, which may finally see the long-held promises finally achieved.