The conjugation of inorganic materials with biological systems has attracted research interest, as a consequence of the availability of the sol–gel process, operating under experimental conditions compatible with biomolecules and whole cells. In Section 2, the merits and limitations of alkoxide-based sol–gel silica as an immobilization material are presented and discussed with particular attention to the confinement of living cells and cell clusters. Biosil technology is based on the encapsulation of whole cells by a sol–gel silica layer deposited on the cell surface using silica precursors in the gas phase. It is presented in Section 3, which describes some important Biosil features such as mechanical stability, versatility for porosity control with the aim of immunological protection, and maintenance of cell viability with free expression of cell functions. Some recent unpublished results are presented to substantiate the properties of Biosil materials for encapsulation of functional animal cells. Extension of the Biosil process to alginate microencapsulation is then presented in Section 4, with emphasis on biocompatibility within the perspective of cell grafts and therapy. Section 5 covers some clinical transplantations concerning grafts with allogenic pancreatic islets and adenovirus infected cells. The conclusions (Section 6) present some potential guidelines for future trends, specifically for whole cell immobilization by silica and, more in general, for advanced biomaterials.