Abnormalities of the endocrine system, and of the hypothalamus-pituitary-adrenal (HPA) axis in particular, are associated with HIV infection. Opportunistic pathogens, neoplasms, and drugs used to treat infections may all contribute to the reported abnormalities, which range from subtle subclinical disturbances of HPA axis regulation to frank adrenal insufficiency. Patients with AIDS should be considered to be at high risk for primary or secondary adrenal insufficiency, and those with symptoms should be evaluated. Subclinical abnormalities may progress to clinically significant adrenal insufficiency as therapies improve and patients with AIDS live longer.