During the past decades, much effort has been made to find efficient alternative solutions to prevent and/or disrupt the adhesion of fouling organisms to surfaces. The use of enzymes emerges among the investigated approaches as one of the favorite candidate antifouling technologies due to enzymes' biodegradability and affordable prices. An overview of the different enzymatic antifouling strategies is presented, highlighting the most promising groups of enzymes, and their utilization upon surface-confinement to control biofouling. While the main strategies to control marine biofouling include the degradation of secreted adhesives and the production of antifouling compounds, the main concepts to control pathogenic biofilms are based on cell lysis and on the degradation of extracellular matrix polymers. Although immobilization can improve enzyme stability, activity and antifouling performance, up to date relatively few scientific articles concerning the use of immobilized enzymes to control biofouling have been published. The successful incorporation of enzymes into coatings yielding surfaces with broad antifouling spectrum and long-term efficacy remains a challenge.