Although many treatments are available for genital warts caused by human papillomavirus (HPV), none are uniformly successful in the treatment of this disease. Most current treatment options work by destroying affected tissue, either by a cytotoxic or a physically ablative mode of action. Interferons have antiviral, antiproliferative, and immunomodulatory activities, but these have not translated into a high level of cure rates against warts. With all current treatments, recurrent warts are common. Therapies currently being investigated include a 5-fluorouracil/epinephrine collagen gel that achieves high concentrations of 5-fluorouracil at the site of injection. Other new treatment modalities focus on activating the host's immune system or improving the delivery of therapeutic compounds to the affected site. Imiquimod, a novel immune-response modifier, induces interferon and a number of other endogenous cytokines. A cream formulation containing 5% imiquimod resulted in good total clearance rates and generally tolerable side effects in controlled clinical trials of patients with external genital warts. Perhaps the most effective means for managing HPV disease would be a vaccine that prevents the occurrence of genital warts. Although it is unlikely that such a vaccine will be introduced in the near future, preliminary studies indicate that it may be possible to develop suitable prophylactic and therapeutic vaccines.