Background: Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or intralesionally in several virally induced cutaneous diseases. Objective: Our purpose was to review the usefulness of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir-resistant strains), Kaposi’s sarcoma–associated herpesvirus, and molluscum contagiosum. Methods: We performed a review of recent literature. Results: Cidofovir is a potent topical intralesional antiviral agent with activity against several DNA viruses that cause cutaneous disease. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. Conclusion: The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in a limited number of patients including those infected with HIV. Although larger studies will be necessary to determine the specific function that topical cidofovir will have in the treatment of cutaneous diseases caused by DNA viruses, the drug offers significant promise. (J Am Acad Dermatol 1998;39:741-5.)