Voriconazole is useful for the treatment of invasive aspergillosis infections; however, metabolism in the liver by prominent cytochrome P450 enzymes makes it vulnerable to clinically significant drug interactions. In addition, enzyme induction leads to changes in voriconazole metabolism even after discontinuation of the offending agent. We report on the case of a 39-year-old man previously receiving phenobarbital, a known inducer of voriconazole metabolism, with an invasive aspergillosis brain infection. Voriconazole levels were obtained to help ensure that the patient receivedadequate antifungal coverage with voriconazole while hepatic enzyme induction waned. This case highlights the importance of proactive management of drug interactions with voriconazole.