The management of clinically resistant or relapsing cytomegalovirus (CMV) is an emerging therapeutic challenge in patients with advanced HIV infection. The efficacy and tolerability of ganciclovir-foscarnet association has been evaluated in the treatment of severe CMV disease (retinitis in two subjects, systemic disease in the remaining patient), which proved refractory to prior single drug chemotherapy in two cases out of three. A literature review of all patients receiving associated ganciclovir-foscarnet for the treatment of AIDS-related CMV disease is presented, and current perspectives of the antiviral treatment of CMV infection in the immunocompromised host are discussed.