Over the last 20 years, the frequency of life-threatening, invasive fungal infections has risen dramatically, corresponding to an increase in the number of immunocompromised patients. Thus, the development of newer, better tolerated, more effective antifungal drugs has become critically important. Voriconazole was the first second-generation triazole to be approved by the US FDA and the EMEA, both in 2002. Voriconazole is currently approved for the treatment of invasive aspergillosis, candidemia, candidal esophagitis and disseminated candidiasis in adults, and serious fungal infections due to Scedosporium apiospermum and Fusarium species. In addition to providing an alternative treatment option for Candida infections and many emerging and refractory invasive fungal infections, voriconazole is currently the treatment of choice for invasive aspergillosis. Voriconazole has excellent in vitro activity against a wide spectrum of yeasts and molds, with only a few notable exceptions. Although it has the potential for some unique and interesting side effects, as well as important drug-drug interactions, the use of therapeutic drug monitoring can be used to optimize its efficacy and safety.