The nanostructure of three bioactive materials, two sol−gel glasses in the SiO2−CaO and SiO2−CaO−P2O5 systems and a SiO2−CaO−poly(dimethylsiloxane) organic−inorganic hybrid, has been studied for the first time by high-resolution transmission electron microscopy. The nanostructural characterization indicates that the addition of P2O5 to the glass leads to crystallization of a silicon-doped calcium phosphate, while in the materials without any phosphorus contentbinary glass and hybridcalcium is located in an amorphous silica network. The different rates of positive bioactive response of both glasses (with and without phosphorus) are strongly correlated with their nanostructure since the distances between [SiO44-] tetrahedra decrease when calcium is not present in the vitreous network and phosphorus bonds to calcium to form a silicon-doped calcium phosphate.