Cytomegalovirus (CMV) retinitis typically presents as a hemorrhagic, full-thickness retinitis in immunosuppressed individuals, often in the setting of human immunodeficiency virus (HIV) infection. The management of CMV retinitis includes systemic and locally administered intravitreal antiviral agents (ie, foscarnet sodium and ganciclovir sodium) and the surgical intravitreal ganciclovir implant. In chronically immunosuppressed patients (ie, transplant recipients and patients undergoing cancer chemotherapy) and in patients with HIV/AIDS who do not immune reconstitute, long-term CMV prophylaxis with valganciclovir hydrochloride may lead to ganciclovir- and foscarnet-resistant CMV strains. Moreover, the identification of drug-resistant CMV may affect the choice or dosing of antiviral medication.1,2 Ganciclovir resistance is classified into genotypic resistance, defined as CMV DNA harboring a mutation known to confer antiviral resistance, or phenotypic resistance, meaning that ganciclovir at a therapeutic dose does not exceed the concentration required to inhibit 50% of CMV growth on viral culture media. We characterize a series of patients with CMV retinitis who were evaluated for genotypic ganciclovir resistance using polymerase chain reaction (PCR)–based analysis of ocular fluids and describe its effect on management.