The search for antifungal agents with acceptable toxicity profiles led first to the discovery of ketoconazole, the first azole-based oral treatment of systemic fungal infections, in the early 1980s. Later, triazoles fluconazole and itraconazole, with a broader spectrum of antifungal activity and improved safety profile were developed. In order to overcome limitations such as sub-optimal spectra of activity, drug-drug interactions, toxicity, development of resistance and unfavorable pharmacokinetics, analogues were developed. Second-generation triazoles, including voriconazole, posaconazole and ravuconazole, are more potent and more active against resistant pathogens.