Immobilization of biomolecules in porous supports, especially in silica matrices, is probably one of the most successful processes in biomaterials synthesis in the last three decades. The flexibility and versatility offered by the sol-gel process, ensured its leading position in the biomolecules immobilization. Functionalization with organic groups of the silica precursors leads to so-called organically modified silica gels. While there are many studies published recently about organically modified silica gels, the relationship between the functionalized support properties and the biomolecules activity is still poorly understood. The aim of this review is to summarize the available results on the influence of the organic functionalization of the silica support on the performance of immobilized biomolecules.