Neurosyphilis is caused by the spirocheteTreponema pallidum. These organisms divide slowly, requiring long exposure to antibacterials for treatment success. In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance. Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis.