Ocular herpes is a prevalent and recurrent eye infection. Without therapy, only one half of non-complicated herpetic corneal surface infections resolve in two weeks. Several treatments, ranging from medications to superficial wiping, aim to shorten the course of herpetic infection of the corneal surface. This review provides evidence-based guidance on the comparative effectiveness of interventions for herpes simplex virus (HSV) epithelial keratitis, by systematically analysing clinical trials from Europe, North America, Asia, Australia, and Africa. Corneal healing rates were examined during treatment with antivirals, interferon, or corneal surface débridement. The first topical nucleoside antiviral drugs, idoxuridine and vidarabine, were moderately effective but newer antiviral drugs such as trifluridine and acyclovir were better. Ophthalmic preparations of trifluridine, acyclovir, ganciclovir, and brivudine were nearly equivalently effective and allowed approximately 90% of treated eyes to heal within two weeks. In parallel with the development of nucleoside antiviral drugs, interferon, which is an antiviral protein of the immune defence system, was studied in trials that indicated effectiveness of topical formulations. Compared with antiviral treatment, the combination of interferon with a nucleoside antiviral agent seemed to facilitate early healing. Ocular allergic and toxic effects were infrequent and transitory. Before the introduction of antiviral drugs and interferon, the corneal surface was removed by physical scraping or chemical erosion, but evidence is lacking that establishes the efficacy and safety of physicochemical methods of débridement. The joint use of débridement and antiviral therapy promoted corneal recovery but was not better than single antiviral medications on corneal epithelial healing.