Food contamination by pathogenic and spoilage bacteria causes approximately 47 million cases of foodborne diseases in the United States and leads to tons of food spoilage, worsening the food loss situation worldwide. In addition, conventional preservation treatments implemented in the food industry decrease food’s nutritional and organoleptic quality. Therefore, there is a need for new alternatives to counteract food contamination without altering its characteristics. Endolysins are a promising strategy due to their unique properties, such as host specificity, synergism with other antibacterial agents, mode of action, and low probability of resistance development. These characteristics differentiate them from other antibacterial agents used in the food industry. Endolysins are enzymes produced by bacteriophages during the process of bacterial infection and lysis. This review describes the advances related to endolysin application systems in food, considering their potential for food safety and an overview of the application conditions according to the type of food and bacteria to be controlled. We also highlight the need for new studies on endolysin encapsulation and prolongation of the action time in cases of outbreaks that allow obtaining key information to improve the application of endolysins in different food matrices during food processing and storage