Infections with non-tuberculous mycobacteria (NTM) belong to the AIDS-defining illnesses of HIV infection. Severe immunosuppression with CD4+ lymphocyte counts lower than 50 cells/microl is a risk factor for the acquaintance of NTM infections. More than 90% of NTM infections in HIV-seropositive individuals are caused by bacteria of the M. avium complex. The manifestations of the disease are heterogeneous and not specific for the causative mycobacterial species. Furthermore, the differentiation between infection and colonisation can be challenging, especially when NTM are isolated from respiratory specimen. Diagnosis and therapy are recommended according to the guidelines of the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA). The treatment success relies on the effects of antiretroviral therapy and a combination of 2 - 4 antimycobacterial antibiotics tailored to the NTM species. In vitro resistance testing often does not predict the clinical response. Interactions with antiretroviral medications are common. The complexity of HIV/NTM co-infection is discussed from an epidemiological, microbiological and clinical perspective.