As CMVR continues to affect HIV-positive and non-HIV immunosuppressed patients, ophthalmologists must continue to tailor diagnostics and therapeutics to individual cases. In HIV-related disease, ocular fluid sampling and intravitreal drug delivery are considerations, but systemic antiviral therapy is paramount in the initial management from both ophthalmic and systemic morbidity standpoints. Non-HIV-related disease should be approached with a multidisciplinary team, including an ophthalmologist/vitreoretinal/uveitis specialist for consideration of intravitreal antiviral therapy with qualitative and quantitative aqueous PCR monitoring, and consideration of PCR genome sequencing for CMV strains that may become resistant to antiviral therapies from long-term antiviral prophylactic exposure. Hematologists or oncologists may help with patients who remain bone marrow-suppressed following transplantation or systemic chemotherapy. Because of related toxicities of the anti-CMV medications and immunosuppressive medications (eg, bone marrow suppression and cytopenias), infectious disease consultation can help in the treatment and monitoring of side effects.