Superficial fungal infections are commonly encountered in dermatologic practices. Their incidence is increasing because of the use of immunosuppressive drugs, an aging population, and the increased prevalence of diabetes mellitus and human immunodeficiency virus (HIV) infection. Topical antifungal therapy typically has been the treatment of choice for uncomplicated dermatophytoses of the skin, such as tinea pedis and tinea cruris. However, these infections may be particularly difficult to treat in high-risk patients, such as those who have diabetes or who are HIV positive. In patients with HIV, dermatophytoses tend to be more extensive and generally require oral antifungal therapy. The allylamine terbinafine has a proven safety record and no significant drug interactions. We review the clinical experience with terbinafine in diabetic and HIV-positive subjects and conclude that terbinafine is safe and has a low drug interaction potential in these high-risk cohort studies.