Major challenges in drug formulation are the poor solid state stability of drug molecules, poor dissolution/ solubility and/or poor pharmacokinetic properties (bioavailability), which may lead to unreliable in vitro-in vivo (IVIV) correlation. To improve current therapeutical strategies, novel means to deliver poorly water soluble active pharmaceutical ingredients, as well as to target them to specific sites or cells in the body are needed. Biomedical applications of porous silicon (PSi) have been actively investigated during the last 10 years, especially in the areas of drug delivery and imaging, due to the biocompatibility and biodegradability of PSi materials, which makes them a potential candidate for controlled drug release. In addition, the unique pore sizes and easily functionalized surface properties of PSi materials allow high drug payloads and controlled kinetics from the drug release formulations. Modification of the PSi surface properties also facilitates biofunctionalization of the surface and the possibility to attach targeting moieties (e.g., antibodies and peptides), thus enabling effective targeting of the payload. In this review, we briefly address the production methodologies of PSi, and we will mainly present and discuss several examples about the biocompatibility of PSi, the most recent in vitro and in vivo applications of PSi as a carrier in drug/protein/peptide delivery and tissue engineering, as well as PSi as a platform for drug targeting and imaging.