Magnetic nanocomposites are hybrid structures consisting of an iron oxide (Fe3O4/γ-Fe2O3) superparamagnetic core and a coating shell which presents affinity for a specific target molecule. Within the scope of phosphopeptide enrichment, the magnetic core is usually first functionalized with an intermediate layer of silica or carbon to improve dispersibility and increase specific area, and then with an outer layer of a phosphate-affi nity material. Fe3O4-coating materials include metal oxides, rare earth metal-based compounds, immobilized-metalions, polymers, and many others. This chapter provides a generic overview of the different materials that can be found in literature and their advantages and drawbacks.