Since the 1950s there has been an increase in the incidence of invasive fungal disease. The first successful systemically administered antifungal drug, amphotericin B, was introduced in the 1950s and, until very recently, was considered the best therapeutic drug for severe mycoses. The development of new antifungals to treat systemic disease has been slow compared to that of antibacterial compounds, with the introduction of only a single new class of drugs over the past 20 years. This review discusses the antifungal drugs that are clinically in use and summarizes interesting new applications and patents from the US Patent and Trademark Office.