Listeria monocytogenes is a foodborne opportunistic pathogen capable to switch from an environmental saprophyte to a potentially fatal human pathogen. The fact that the pathogen maintains the genes suitable for an elaborate infectious process indicates that these genes are required to survive in the environment. However, no environmental host reservoir for L. monocytogenes has been identified so far. The similarity of free-living, bacteria-scavenging amoebae to macrophages led to the hypothesis that protozoa may represent the missing link in the ecology and pathology of L. monocytogenes. Consequently, numerous studies have been published reporting on the potential of Acanthamoeba spp. to serve as host for a variety of pathogenic bacteria. However, the data on the interaction of L. monocytogenes with Acanthamoeba spp. are inconsistent and relatively little information on the impact of this interaction on growth and distribution of the foodborne pathogen is currently available. Hence, this review focuses on the interaction of L. monocytogenes and Acanthamoeba spp. affecting survival and growth of the foodborne pathogen in natural and man-made environments, in order to highlight the potential impact of this interplay on food safety and human health.