In the last decade, new trends for enzyme attachment to solid carriers have emerged in an attempt to rationalize the classical methods for enzyme immobilization. In silico analysis is becoming a powerful tool to predict the orientation of enzymes covalently attached to the carrier or the protein regions involved in adsorption to the support. Significantly, an array of algorithms has been established for the rational design of immobilized derivatives, which comprises both the protein size and the textural properties of the support. Ordered mesoporous materials open a challenging pathway to tailor immobilized enzymes with high volumetric activity and minimum lixiviation. In addition, fluorescence confocal microscopy is being successfully employed to understand the diffusional restrictions and the distribution of biomolecules within the support.