Many advances have been made in antifungal therapy over the last three decades. Itraconazole and fluconazole, two investigational triazole agents, are the most recent additions to the list of antifungal drugs. This review has focused primarily on their mechanisms of action, favorable pharmacologic properties, and spectra of activity against a broad range of systemic pathogens. Itraconazole and fluconazole show much promise as orally active agents, with less potential for toxicity than the currently available azoles. Fluconazole and, to a lesser degree, itraconazole are especially promising therapies for cryptococcal meningitis. In addition, fluconazole may prove to be highly effective in urinary tract infections caused by Candida species and other fungi. Ongoing and future clinical trials will more clearly define the specific roles of itraconazole and fluconazole in the treatment of systemic mycoses.