Voriconazole is an extended-spectrum triazole antifungal with activity against a wide variety of pathogens, including Aspergillus, Candida, Cryptococcus neoformans, Fusarium, and Scedosporium. It exerts its antifungal activity by blocking the synthesis of fungal cell membranes and is considered the first-line treatment for invasive aspergillosis. Because the pharmacokinetics of voriconazole can demonstrate considerable variability, it has been suggested that monitoring plasma levels of voriconazole may play an important role in optimizing the efficacy and safety of the drug in complex patients like those at risk of or who have invasive aspergillosis. In this article, we review the criteria for therapeutic drug monitoring and assess the evidence for using plasma voriconazole concentrations to individualize doses in children.