Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. This disease is highly endemic in some regions of North America, Central America, and South America and is also reported in certain countries of Asia and Africa. It often affects people with impaired immunity, including people living with HIV, among whom the most frequent clinical presentation is disseminated histoplasmosis. The symptoms of disseminated histoplasmosis are non-specific and may be indistinguishable from those of other infectious diseases, especially disseminated tuberculosis (TB), thus complicating diagnosis and treatment. Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region. These guidelines aim to provide recommendations for the diagnosis, treatment, and management of disseminated histoplasmosis in persons living with HIV