Human adenovirus (HAdV) is a ubiquitous virus that infects the mucosa of the eye. It is the most common cause of infectious conjunctivitis worldwide, affecting people of all ages and demographics. Pharyngoconjunctival fever outbreak is due to HAdV types 3, 4, and 7, whereas outbreaks of epidemic keratoconjunctivitis are usually caused by HAdV types 8, 19, 37, and 54. Primary cellular receptors, such as CAR, CD46, and sialic acid interact with fiber-knob protein to mediate adenoviral attachment to the host cell, whereas adenoviral penton base–integrin interaction mediates internalization of adenovirus. Type 1 immunoresponse to adenoviral ocular infection involves both innate immunity mediated by natural killer cells and type 1 interferon, as well as adaptive immunity mediated mainly by CD8 T cells. The resulting ocular manifestations are widely variable, with pharyngoconjunctival fever being the most common, manifesting clinically with fever, pharyngitis, and follicular conjunctivitis. Epidemic keratoconjunctivitis, however, is the severest form, with additional involvement of the cornea leading to development of subepithelial infiltrates. Because there is currently no US Food and Drug Administration-approved treatment for adenoviral ocular infection, current management is palliative. The presence of sight-threatening complications following ocular adenoviral infection warrants the necessity for developing antiadenoviral therapy with enhanced therapeutic index. Future trends that focus on adenoviral pathogenesis, including adenoviral protein, which utilize host receptors to promote infection, could be potential therapeutic targets, yielding shorter active disease duration and reduced disease burden.