Retinitis due to cytomegalovirus (CMV) infection is a widely recognized complication of advanced disease due to human immunodeficiency virus type 1 (HIV-1). Less appreciated are other neurological manifestations of CMV infection in persons with AIDS. Dr. J. Allen McCutchan has comprehensively reviewed the various clinical presentations of CMV neurological disease as well as the methods of diagnosis, the neuropharmacology of available antiviral agents, the results of therapy, and the potential for prevention of these sequela of advanced immunosuppression. As the ability to prevent diseases such as Pneumocystis carinii pneumonia, bacteremia secondary to Mycobacterium avium, tuberculosis, serious fungal infections, and toxoplasma cerebritis is increasing, physicians must now treat more HIV-1-infected persons with CMV disease. This AIDS Commentary provides a timely update of the current state of our knowledge regarding this serious problem.