Listeria monocytogenes is a ubiquitous Gram-positive bacterium widely distributed in the soil where it lives as a saprophyte. This opportunistic pathogen causes listeriosis in humans through consumption of contaminated food especially ready-to-eat (RTE) food, chiefly deli meat, cheese, and smoked fish. Pregnant women, neonates, the elderly, and immunocompromised patients are especially vulnerable to listeriosis. The pathogenesis of listeriosis begins with ingestion of the bacterium by humans; low pH and increased gastric temperature in the gastrointestinal system upregulates the production of virulence proteins, for example PrfA and internalins, facilitating the transition of L. monocytogenes from its saprophytic existence to a pathogenic one. Internalins mediate its adherence and invasion of host intestinal epithelial cells which are usually non-phagocytic. Inside the phagosome, the low carbohydrate and low iron concentration suppress internalin production. The production of listeriolysin O (LLO) and PlcA then allows the lysis of the phagocytic vacuole, enabling the entry of bacteria into the cytosol. High levels of ActA and PlcB expression promotes cell-to-cell spread. Understanding the pathogenesis of L. monocytogenes can help appreciate the microbial virulence, treatment options, and the development of better therapeutic agents for infected patients. Therefore, this review focuses on the pathogenesis L. monocytogenes, as well as the clinical characteristics, and therapeutic regimens that would be beneficial in the management of the disease.