Opportunistic infections are major causes of morbidity in patients with human immunodeficiency virus (HIV) infection. Penicillium marneffei infection is very common in HIV-infected individuals in northern Thailand. The patients usually present with fever, anemia, weight loss, skin lesions, generalized lymphadenopathy, and hepatomegaly. The average number of CD4+ T-lymphocytes at presentation was 63.8 cells/mm3. Diagnosis depends on familiarity with the clinical syndromes and support from the mycology laboratory. The response to antifungal treatment of the patients is generally good, but depends on the ability of the physician to make the diagnosis and start the treatment early. New approaches to the laboratory diagnosis of P. marneffei infection have been reported. Further study of these approaches may help physicians in taking better care of the patients.