Listeria monocytogenes is an opportunistic foodborne pathogen causing listeriosis, an often fatal infection leading to meningitis, sepsis, or infection of the fetus and abortion in susceptible individuals. It was recently found that the bacterium can also cause acute, self-limiting febrile gastroenteritis in healthy individuals. In the intestinal tract, L. monocytogenes penetrates the mucosa directly via enterocytes, or indirectly via invasion of Peyer's patches. Animal models for L. monocytogenes infection have provided many insights into the mechanisms of pathogenesis, and the development of new model systems has allowed the investigation of factors that influence adaptation to the gastrointestinal environment as well as adhesion to and invasion of the intestinal mucosa. The mucosal surfaces of the gastrointestinal tract are permanently exposed to an enormous antigenic load derived from the gastrointestinal microbiota present in the human bowel. The integrity of the important epithelial barrier is maintained by the mucosal immune system and its interaction with the commensal flora via pattern recognition receptors (PRRs). Here, we discuss recent advances in our understanding of the interaction of L. monocytogenes with the host immune system that triggers the antibacterial immune responses on the mucosal surfaces of the human gastrointestinal tract.