Objective: To review the nature of the presentation of neurosyphilis, the value of diagnostic tests, and the classification of the disease. Methods: A retrospective review was carried out of the records of patients who had been identified as possible cases of neurosyphilis by a positive FTA-abs test in the CSF. The review extended over 10 years at a single hospital which served a population of mixed ancestry in a defined catchment area in the Western Cape province of South Africa. Patients were placed in predefined diagnostic categories, and clinical, radiological, and laboratory features were assessed. Results: 161 patients met diagnostic criteria for neurosyphilis: 82 presented with combinations of delirium and dementia and other neuropsychiatric conditions, and the remainder had typical presentations such as stroke (24), spinal cord disease (15), and seizures (14). The average age of presentation ranged from 35.9 to 42.6 years in the different categories of neurosyphilis. Of those followed up, 77% had residual deficits from their initial illness. Cerebrospinal fluid (CSF) VDRL was positive in 73% of cases. Conclusions: The diagnosis of neurosyphilis can be made with reasonable certainty if there is an appropriate neuropsychiatric syndrome associated with a positive CSF VDRL. If the VDRL is negative, a positive FTA-abs in an appropriate clinical setting, associated with raised CSF cell count, protein, or IgG index, is a useful method of identifying neurosyphilis. Tabes dorsalis has become uncommon, but this is likely to be the only manifestation of neurosyphilis that has been altered during the antibiotic era.