Anogenital condyloma acuminatum (genital warts) is the most commonly diagnosed sexually transmitted viral disease in the United States. At least 14 of the more than 60 types of human papillomaviruses (HPVs) are responsible for condyloma acuminatum. Anogenital condyloma acuminatum has a broad spectrum of manifestations in men and women, including subclinical latent infection, clinically apparent warts, abnormal genital cytology and squamous carcinoma. Traditional therapeutic modalities include cytolytic chemical agents and ablative techniques. These anti-wart methods are used in an attempt to eliminate clinically apparent disease. However, they are associated with high rates of recurrence because they do not eradicate the subclinical or latent reservoir of HPV remaining in adjacent epithelial cells and mucous membranes. Immunologic therapy with interferons (IFNs) represents a promising new antiviral modality that can be directed against all sites of infection, including clinical, subclinical and latent disease. IFN-alpha, IFN-beta and IFN-gamma are the three major groups of IFNs. These three groups of IFNs have been used successfully as monotherapy or in combination with traditional modalities to treat anogenital condyloma acuminatum. This review focuses on IFN-alpha, IFN-beta and IFN-gamma therapy of anogenital HPV infections.