A number of striking changes have occurred recently in the presentation and course of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) who are receiving highly active antiretroviral therapy (HAART). Before the use of HAART, CMV retinitis was the most common intraocular infection in patients with AIDS, occurring in up to 40% of patients, typically when CD4+ cell counts have decreased to less than 0.10 x 10(9)/L. By studying CMV retinitis, clinicians can investigate whether the rejuvenated immune system that results from HAART can effectively control opportunistic infections in patients with AIDS. In some patients, retinitis has not progressed when specific anti-CMV therapy was discontinued, but a number of patients have developed substantial intraocular inflammation, which has resulted in decreased visual acuity. Anterior uveitis, cataract, vitritis, cystoid macular edema, epiretinal membrane, and disc edema may occur in patients with CMV retinitis who have experienced HAART-associated elevation in CD4+ cell counts. Since immune recovery uveitis does not occur in eyes without CMV retinitis, the ocular inflammation appears to be related to the CMV infection. Anti-CMV maintenance therapy likely can be safely discontinued in some patients with CMV retinitis if CD4+ cell counts are stable or increasing and have been higher than 0.10 x 10(9)/L for at least 3 months. Immune recovery in patients receiving HAART has been effective in controlling opportunistic infections, but it may also result in intraocular inflammation, which can have adverse effects on the eye.