HIV and syphilis affect similar patient groups and co-infection is common. All patients presenting with syphilis should be offered HIV testing and all HIV-positive patients should be regularly screened for syphilis. Syphilis agent may enhance the transmission of the other, probably through increased incidence of genital ulcers. Detection and treatment of syphilis can, therefore, help to reduce HIV transmission. Syphilis may present with non-typical features in the HIV-positive patient: there is a higher rate of symptomless primary syphilis and proportionately more HIV-positive patients present with secondary disease. Secondary infection may be more aggressive and there is an increased rate of early neurological and ophthalmic involvement. Diagnosis is generally made with serology but the clinician should be aware of the potential for false-negative serology in both primary and, less commonly, in secondary syphilis. All HIV-positive patients should be treated with a penicillin-based regimen that is adequate for the treatment of neurosyphilis. Relapse of infection is more likely in the HIV-positive patient and careful follow-up is required.