The incidence of cytomegalovirus (CMV) retinitis appears to be declining with improved treatment protocols for HIV and prophylaxis protocols for other high risk patients. Despite this, CMV retinitis remains a major cause of visual loss in patients who are severely immunocompromised. Treatment options are evolving in the light of viral resistance, new methods of drug delivery, new drugs, and the increased potential for improvement of immune function that modern antiretroviral therapy provides. In this article, we review the changing options available for the management of CMV retinitis and discuss possible therapeutic agents for the future.