Human Immunodeficiency Virus (HIV) infection represents one of the most serious challenges to global public health, since more than 30 million people are living with HIV/AIDS worldwide. Highly active antiretroviral treatment (HAART) introduction has dramatically changed the mortality and morbidity of HIV-affected subjects in industrialized countries but has implied an evolution of many HIV-related aspects, both in the utilisation of new antiretroviral drugs options and in the newly-observed spectrum of HIV-associated diseases, including the rheumatic pathology. Current epidemiological, therapeutic, autoimmune and rheumatic aspects of HIV-1 infection are here discussed.