While infectious diseases clinicians have been schooled in syphilology for generations, new aspects of syphilis continue to appear. Such is the casein HIV-infected individuals, in whom the clinical, diagnostic, and therapeutic implications are quite confusing. Dr. Edward W. Hook III, associate professor of medicine at The Johns Hopkins University School of Medicine, has been one of the front-runners in examining and describing new aspects of this age-old infection. In this AIDS Commentary he discusses the critical clinical questions relevant to syphilis in persons with HIV infection.