Silicon nanostructures have properties that make them appealing for applications in biomedicine and biotechnology. The fabrication and characterization of silicon nanostructures are currently gaining a lot of attention and they can include nano-wires, whiskers, pillars, tubes, cones, particles, etc. There are several methods to assist the generation of these nanostructures like laser ablation, thermal evaporation decomposition, and chemical vapor deposition, among others. We consider they are highly potential tools for the improving of diagnosis techniques and the treatment of important biological conditions. The objective of this review is to summarize the main aspects of the physicochemical design of silicon nanomaterials, in addition to toxicological considerations regarding biocompatibility, biodistribution and cell dynamics. Finally, we emphasis on important biomedical applications, such as gene therapy, drug delivery, imaging and sensoring.