Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Although uncommon, it should be considered among the list of important opportunistic infections in severely immunocompromised patients. Patients living with AIDS are at particular risk of disseminated histoplasmosis. Diagnosis requires a high level of clinical suspicion. The infection is best confirmed by demonstration of the organism in tissue specimens or by culture. Amphotericin B is the most effective drug for severe disseminated histoplasmosis. Response is good but life-long maintenance is required to prevent relapse.