Onychomycosis is a common disease of the nail unit caused by dermatophytes, yeasts, and molds. In more than 80% of cases, onychomycosis is caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The prevalence of onychomycosis in the world’s population is 2% to 18% or higher and accounts for approximately 50% of all nail disorders. Until recently, available therapies were inadequate because of low cure rates, high relapse rates, and often dangerous side effects. An increased understanding of nail pharmacokinetics has led to the development of safer, more effective systemic therapies for onychomycosis, such as itraconazole, fluconazole, and terbinafine. These new oral antifungal agents allow shorter periods of treatment, provide rapid efficacy, and may improve patient compliance and attitudes regarding therapy. Treatment selection will depend on several factors, including appropriate spectrum of activity, adverse effects, and potential drug interactions plus patient preferences for specific dosing regimens. (J Am Acad Dermatol 1999;40:S21-6.)