In the present era of highly active antiretroviral therapy (HAART), the challenges that HIV/AIDS patients face with regard to ocular complications has changed immensely; nonetheless, significant ocular morbidity persists. We present an update on these challenges, focusing particularly on the relevant literature from the past 12-18 months. Although its incidence has decreased substantially in the HAART era, cytomegalovirus (CMV) retinitis remains an important cause of ocular morbidity and predictor of mortality. Presently, patients with less than 50 CD4 T-cells/μL have an approximately equal risk of developing this potentially blinding ocular complication compared with the pre-HAART era. Less is understood about the current epidemiological considerations of ocular syphilis and HIV; however, patients with HIV may have increased likelihood of posterior syphilitic uveitis. Regarding the neuroretinal disorder associated with HIV, new ophthalmic imaging modalities are helping to uncover potentially associated structural alterations. Future challenges in the fight against HIV/AIDS-related eye disease will involve identifying additional factors conferring increased risk of CMV retinitis, understanding the scope of ocular syphilis and other eye infections in HIV patients, and furthering our understanding of the structural changes in neuroretinal disorder as an indicator of other end-organ damage.