It is still not quite well understood why there is no optimal or even a satisfactory antibiotic therapy for listeriosis. Although almost all Listeria strains that induce sepsis, meningitis and encephalitis, as well as many other manifestations--in particular, in immunocompromised individuals--are susceptible to most of the common antibiotics, the cure rate is only approximately 70%. The most effective regimen still consists of a combination of an aminopenicillin (amoxicillin or ampicillin) plus an aminoglycoside. In vitro, this combination is bactericidal, whereas aminopenicillin alone only exerts a weak bactericidal activity against Listeriae. These antibiotics only poorly penetrate the cerebrospinal fluid and thus, only high doses given over a prolonged period of 2-3 weeks are curative. Furthermore, Listeria monocytogenes belongs to the group of facultative intracellular bacteria, which means that a certain population is inaccessible for antibiotics. Theoretically, a drug which is endowed with bactericidal activity superior to that of ampicillin would be preferable. Furthermore, the candidate drug should easily cross the blood-brain barrier into the CNS, be able to accumulate within host cells, reach the cytoplasm and be active under these unusual conditions. Because of all these arguments, the new quinolones are of particular interest; but broad clinical data are still lacking. It is unclear as to whether antibiotics alone will be sufficient to increase the prognosis. Adjunctive therapy with immunomodulators, which are able to reconstitute the defective defence capacities, would presumably create the conditions necessary to finally resolve listeriosis.