Onychomycosis is one of the most stubborn superficial mycoses. With few exceptions, oral antifungal therapy is needed to achieve resolution. Before oral itraconazole, fluconazole, and terbinafine hydrochloride became available, physicians had to rely on prolonged therapy with griseofulvin or oral ketoconazole. Of the newer oral agents, itraconazole appears to have the broadest spectrum of action, with therapeutic activity against dermatophytes, yeasts, and some nondermatophyte molds. Tissue pharmacokinetics accounts for significantly greater efficacy and much shorter treatment courses for fungal infections of the skin and nails. In general, oral itraconazole, fluconazole, and terbinafine are very well tolerated. The newer oral agents offer improved efficacy over griseofulvin and ketoconazole for onychomycosis and dry tinea pedis.