Chitosan has attracted a growing attention as a food preservative due to its versatility, nontoxicity, biodegradability and biocompatibility. This review aims to provide a critical appraisal of the limitations and opportunities of the use of chitosan as a food preservative. The application of chitosan as a food preservative necessitates insights into mechanisms of chitosan-mediated cell death and injury, factors affecting chitosan activity and effects of chitosan on food safety and quality. Chitosan exerts antimicrobial activity by perturbing the negatively charged cell envelope of micro-organisms with its polycationic structure. Intrinsic characteristics, including molecular weight and degree of deacetylation (DD), and other ambient conditions, including pH, temperature and neighbouring components, affect chitosan activity. Because the antimicrobial activity of chitosan is mainly based on ionic interactions with negatively charged components of the bacterial cell envelope, the food matrix can strongly interfere with the antimicrobial activity of chitosan. Despite its limited antimicrobial efficacy, chitosan demonstrates both bactericidal and bacteriostatic effects in specific food products. Moreover, chitosan can also enhance the efficacy of commercial intervention technologies, such as heat and pressure treatment, and aid the preservation of food quality, including retardation of lipid oxidation, weight loss and deterioration in sensory attributes.