In this study we present the results of a therapeutic drug monitoring retrospective analysis involving 14 patients with several underlying diseases who were receiving voriconazole for the treatment of fungal infections. A simple high performance liquid chromatography assay with ultraviolet detection was used in the drug monitoring. We report here that serum concentrations were highly variable and unpredictable in most patients. We also found that lack of response was more frequent in patients with levels persistently lower than 1 mg/l. The number of samples with voriconazole concentrations below 1 mg/l was significantly higher in patients who exhibited therapeutic failures (88% versus 27%; P < 0.001). In addition, the period of time in which voriconazole concentrations were maintained below 1 mg/l was slightly higher in patients in the failure group. We suggest that serum concentration should be individually quantified for patients receiving voriconazole therapy. Further prospective studies are needed to clarify the potential benefit of the individualization of treatment.