A range of topical and systemic therapies exists for treating recurrent herpes labialis. Among the topical agents, aciclovir and its derivatives can lessen the symptoms and duration of disease if applied frequently in the proper vehicle and started during the prodromal phase. Delivering these agents to the lesion via novel devices or vehicles may enhance their topical efficacy in the future. Among the systemic agents, new high-dose, 1-day regimens using either famciclovir or valaciclovir offer greater convenience and cost-effectiveness compared with traditional 5-7-day therapy. Combining either topical or systemic antinucleoside agents with topical anti-inflammatories such as corticosteroids may also lead to enhanced efficacy. Novel agents such as docosanol, toll-like receptor agonists, and viral ribonucleoside reductase inhibitors may also play a larger role in the future.