Listeria monocytogenes is a deadly foodborne pathogen. It is ubiquitous in nature and can be found in the wilderness, in the farm environment, in the food production environment and in food products. Transmission routes are complex and progress from natural environments to contamination of foods and subsequently host infection. The ability of L. monocytogenes to persist in such a large array of habitats relies on gene expression regulation and metabolic features. When contaminated food is consumed, the fate of L. monocytogenes depends on a complex interplay between the composition of the food matrix, host susceptibility as well as strain phylogeny. Indeed, genetic features underlie fitness differences between isolates during the saprophytic lifestyle and during infection.