Herpes simplex virus type 1 (HSV-1) gives rise to a variety of clinical disorders and is a major cause of morbidity and mortality worldwide. HSV-1 infections are common in oral and perioral area. The aim of the present report was to critically examine the published literature to evaluate the advantages and limitations of therapy of HSV-1 infection in both immunocompetent and immunocompromised patients. Systemic antiviral therapy has been widely accepted as effective for primary herpetic gingivostomatitis. Aciclovir (ACV) 5% cream seems to be the accepted standard topical therapy for herpes labialis, being both effective and well tolerated, although penciclovir 1% cream has been proposed as a potentially useful treatment. Systemic ACV may be effective in reducing the duration of symptoms of recurrent HSV-1 infection, but the optimal timing and dose of the treatment are uncertain. Aciclovir and famciclovir may be of benefit in the acute treatment of severe HSV-1 disease in immunocompromised patients. There is also evidence that prophylactic oral ACV may reduce the frequency and severity of recurrent attack of herpetic infection in immunocompromised patients, but the optimal timing and duration of treatment is uncertain and can vary in different situations.