Porous silica-based materials have burgeoning applications ranging from fillers and additives, to adsorbents, catalysts, and recently therapeutic agents and vaccines in nanomedicine. The preponderance of these materials is made by sol-gel processing wherein soluble silica precursors are reacted to form amorphous networks composed of siloxane bonds. The facile sol-gel approach allows for an unlimited variety of binary tertiary and more complex chemical compositions including organic ligands and networks resulting in so-called organic-inorganic hybrid materials. Here, a brief review of the recent progress in sol-gel-derived silica materials prepared as particles, thin films, biosilica/silica bioreplicas (of molecules, cells and organisms), and their related preparation, properties, and bioapplications is provided. First, it highlights the recent achievements of mesoporous silica nanoparticles in biomedical applications, including therapeutic agent delivery, multimodal imaging and theranostics, and bone tissue engineering and repair. Second, the research in evaporation-induced self-assembly (EISA)-based mesostructured silica thin films and cell-directed EISA in bio/nano interfaces for various bioapplications, such as bioactive coatings, biosensing, and living cell immobilization, has been reviewed. Third, the pioneering work in biomimetic silicification/ immobilization of biomolecules and bio-organisms and silica bioreplication of complex bio-organisms is summarized. Finally, it is concluded with personal perspectives on the directions of future work on this field. In 1846, Ebelmen synthesized tetraethylorthosilicate (TEOS) from SiCl 4 and ethanol and exposed it to water forming a transparent glassy material upon gelation and drying (now recognized to be a microporous xerogel). In 1864, the term "sol-gel" was first proposed by Graham during his work on silica sols. [2] In 1912-1915, Patrick developed an economically viable and rapid sol-gel process to mass-produce silica gel from sodium silicate (Na 2 SiO 3). And in 1931, Kistler reported the first synthesis of a highly porous silica (SiO 2) form, termed as "aerogel," which was a porous ultralight material derived from hydrolytic polycondensation of silicic acid (Si(OH) 4) to form a gel followed by supercritical drying to avoid drying shrinkage. [3] All of these efforts can be regarded as the beginning of modern sol-gel based silica materials, which are now ripening for wide range of applications, including the two pillars of the chemistry practice (synthesis and analysis), protective coatings, adsorption, chromatography, separation, biotechnology, energy conservation, cultural heritage restoration, and environmental remediation as well as many other fields of contemporary technology. [4] Based on the breakthroughs in synthesis, the recent two decades have witnessed an exponential increase in research of sol-gel-based silica materials for biomedical applications. Silica is inherently compatible with biological systems and was accepted as "Generally Recognized As Saf...