Metal nanoparticles (Me NPs)-enzyme biohybrids have emerged in recent years as novel nanocomposites that combine the best properties of Me NPs and enzymes. The combination of Me NPs and enzymes generates hybrids that are highly biocompatible and less toxic than Me NPs alone with superior antimicrobial capacity. Their antimicrobial effectiveness lies in their ability to combine the catalytic properties of enzymes with the robust antimicrobial characteristics of metals. In addition, an infinite number of metal-enzyme combinations are possible, employing diverse synthesis methods and resulting in biohybrids with a wide range of properties and applications. In this chapter, the antimicrobial capacity of different Me NP-enzyme hybrids is illustrated as well as their application as coatings or additives on different surfaces.