Endolysins, bacteriophage-encoded enzymes, have emerged as antibacterial agents that can be actively applied in food processing systems as food preservatives to control pathogens and ultimately enhance food safety. Endolysins break down bacterial peptidoglycan structures at the terminal step of the phage reproduction cycle to enable phage progeny release. In particular, endolysin treatment is a novel strategy for controlling antibiotic-resistant bacteria, which are a severe and increasingly frequent problem in the food industry. In addition, endolysins can eliminate biofilms on the surfaces of utensils. Furthermore, the cell wall-binding domain of endolysins can be used as a tool for rapidly detecting pathogens. Research to extend the use of endolysins toward Gram-negative bacteria is now being extensively conducted. This review summarizes the trends in endolysin research to date and discusses the future applications of these enzymes as novel food preservation tools in the field of food safety.