OBJECTIVE: To review the evidence regarding the treatment and prevention of herpes labialis. QUALITY OF EVIDENCE: The evidence relating to treatment and prevention of herpes labialis is derived from randomized controlled trials (level I evidence). MAIN MESSAGE: Treatment with an indifferent cream (zinc oxide or zinc sulfate), an anesthetic cream, or an antiviral cream has a small favourable effect on the duration of symptoms, if applied promptly. This is also the case with oral antiviral medication. If antiviral medicine (cream or oral) is started before exposure to the triggering factor (sunlight), it will provide some protection. Research on sunscreens has shown mixed results: some protection has been reported under experimental conditions that could not be replicated under natural conditions. In the long term, the number of relapses of herpes labialis can be limited with oral antiviral medication. CONCLUSION: Only prompt topical or oral therapy will alleviate symptoms of herpes labialis. Both topical and oral treatment can contribute to the prevention of herpes labialis.