Considering current economical and ecological contexts, the questions of setting up clean and eco-efficient processes as well as saving our energy resources appear to be of fundamental importance. We need to develop reactions that would address the problem of the selective transformation of chemicals under mild conditions. This urges industries to develop “green chemistry” procedures that have not only to include catalytic processes to limit waste, but also to use harmless solvents, the ideal of which would be water, with low temperatures and pressures to limit energy consumption. Such conditions are already fulfilled by enzymes, including metalloenzymes. Because the properties of enzymes are complementary to those of chemical catalysts, it is conceivable to design catalysts that would combine the robustness and wide range of reactions of chemical catalysts with the ability of enzymes to work under mild conditions in aqueous medium and with high selectivity. Many teams have been working on the conception of hybrid biocatalysts, obtained by association of a protein with a synthetic molecule. This chapter reviews the three strategies explored to obtain the kind of hybrid biocatalysts that are artificial metalloenzymes. Catalysis by artificial metalloenzymes in cascade reactions is covered in the last paragraph.