Nocardia infection is a rarely reported opportunistic infection in HIV-infected patients. Nocardiosis typically occurs in HIV-infected patients with advanced immunodeficiency (89% of cases), often as the initial serious opportunistic infection (42% of cases). In most HIV-infected patients, nocardia infection is disseminated at the time of diagnosis and is characterized by an indolent course that may be difficult to differentiate from other systemic infections. Invasive procedures to obtain tissue of fluid for culture are frequently necessary to make the diagnosis, although a Gram or modified acid-fast stain of sputum or other infected material may suggest the etiologic agent. Although trimethoprim-sulfamethoxazole is the most commonly used initial therapy, it was discontinued in 50% of cases because of adverse reactions. Even though the optimal treatment has not been defined, nocardiosis in HIV-infected patients can be treated successfully with or without sulfa-containing antimicrobial regimens, along with surgical drainage when necessary. Recurrence is noted after short duration of treatment, and consideration should be given to lifelong maintenance therapy.