Background: Each day more than 12 000 people worldwide become infected with the HI virus. HIV is distributed mainly among working adults. Two thirds of people with HIV infections are in employment. Methods and Results: The steps taken in the management of HIV-infected healthcare workers (HCWs) in the area of responsibility of the Frankfurt City Department of Health are exceptional and offer a new paradigmatic approach. The stepwise escalation of measures and its impact on Public Health and the prevention of hospital-acquired HIV infections are elaborated and discussed in this article. Presented are examples of recent cases managed according to measures recommended by the expert commission of the German Association for the Prevention and Control of Infectious Diseases (DVV) and the Robert Koch Institute (RKI). Discussion: Healthcare workers with HIV infections pose a significant challenge for occupational health management. The aims are to assure the health status of other employees and to prevent hospital-acquired HIV infections of patients. The occupational health physician plays a key role here. It is necessary to observe the personal and professional rights of the HIV-infected employees and at the same time to prevent virus transmission to patients.