The diagnosis of neurosyphilis is important but remains difficult because of variable clinical features and an unpredictable course. Laboratory confirmation involves a combination of serological tests, none of which alone provides a reliable indication of current disease activity. Although in the UK the incidence of neurosyphilis has fallen steadily, its many manifestations require clinicians to remain alert to the diagnosis, particularly because incidental antibiotic therapy may modify the presenting features. As a sexually-transmitted disease, the diagnosis of syphilis carries great social stigma. The need for informed consent before routine testing, and the provision of psychological support for the patient and carers in the event of a positive diagnosis, must be considered.