Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required.