Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS. Untreated, CMV retinitis is a binding disease. Ganciclovir, a nucleoside analog, and foscarnet, a pyrophosphate analog, are both effective in controlling CMV retinitis. A randomized, controlled, comparative trial of foscarnet and ganciclovir demonstrated that they were equivalent in terms of controlling CMV retinits, but that foscarnet was associated with a longer survival, possibly due to an antiretroviral effect of foscarnet. However, foscarnet was less well tolerated than ganciclovir, primarily due to the nature of its side effects. Because foscarnet and ganciclovir have different side effects, initial treatment of CMV retinitis should be individualized. Newer technological developments, including oral ganciclovir and the ganciclovir intraocular device, may influence the choice of initial treatment, particularly because of their effect on the quality of life when compared to chronic intravenous therapy. The occurrence of relapse and the development of resistance remain long-term concerns, which may alter the use of anti-CMV drugs over time.