Listeria monocytogenes is a Gram-positive bacillus and facultative intracellular bacterium whose transmission occurs mainly through the consumption of contaminated food. Listeriosis has an incidence estimated at around three-six cases per million per year and the most common forms of the infection are neurolisteriosis, bacteraemia, and maternal-neonatal infection. Those affected by listeriosis are at the extremes age of the life or report specific risk factors, such as malignancies, causing a defect of cellular immunity. Patients with L. monocytogenes meningitis present with signs and symptoms similar to those reported in the general population with community-acquired bacterial meningitis, but can experience a longer prodromal phase. Instead, patients with bacteraemia present generally with a febrile illness without focal symptoms, or with influenza-like symptoms and diarrhoea. These aspecific findings make the diagnosis difficult in the population of patients at the highest risk such as cirrhotics or those receiving chemotherapy. Mortality rate is estimated around 20% with a significant increase among those reporting a delay in diagnosis and treatment and in those with severe comorbidity. A number of antibiotics have been demonstrated to be active against L. monocytogenes, but penicillin, amoxicillin, and ampicillin are those used with the highest frequency and suggested by current guidelines and expert opinions. These antibiotics bind to PBP-3 with high affinity and are stored in the cytosol when taken up by cells. Although amoxicillin appears to have a better activity than ampicillin on the basis of in vitro studies, ampicillin is currently the drug of choice for the treatment of listeriosis. Cotrimoxazole could be administered as an alternative treatment; its use is associated with a favourable outcome probably due to the favourable penetration with brain. Quinolones have an excellent tissue and cell penetration and are rapidly bactericidal, but their clinical activity is not as high as we can predict on the basis of experimental model. Linezolid offers a number of advantages in the empiric treatment of meningitis due to its favourable penetration of CSF and the absence of bacteriolytic effect on S. pneumoniae as confirmed by a number of case-series highlighting its use as rescue therapy of pneumococcal meningitis, but data are currently limited particularly if we consider neurolisteriosis. Combination therapies have been proposed to enhance the activity of penicillins against Listeria in an attempt to achieve complete killing and decrease mortality. Steroids use is ineffective.