All opportunistic infections of the eye have their origin in the suppression of the immune system of the host. The immunosuppression can be acquired through the human immune deficiency virus or as a result of immunosuppressive therapy in solid-organ transplant recipients with a maintenance therapy of cyclosporin and prednisone or during chemotherapy in patients with myelo-proliferative disorders. Generally, in less than 2% could severe opportunistic infections of the eye, like cytomegalovirus (CMV) or herpes virus infection, be found in transplant and cancer patients with chemotherapy. About 35–70% of patients with AIDS exhibit ocular manifestations of disease, so the most notable opportunistic infection with an incidence of 35% would be CMV retinitis. Less frequent are progressive outer retinal necrosis syndrome, Kaposi’s sarcoma and optic neuropathies. This paper reviews recent advances in the diagnosis and special local therapies of the worst opportunistic infections in immunocompromised hosts.