The introduction of a standardized set of criteria to define invasive fungal infections has fulfilled a need. The criteria make comparisons between various clinical studies more easy and facilitate discussions of trial designs. However, application of the criteria in practice has indicated that some criteria for possible disease (in particular, antibiotic-resistant fever during neutropenia) are rather unspecific and allow the inclusion of patients who are unlikely to have an invasive fungal infection in trials. On the other hand, new diagnostic tools have been validated sufficiently to consolidate the effect of the criteria on the diagnosis of invasive fungal infections. Finally, it has become evident that changing medical practices with deleterious consequences for the innate immune system extend the population at risk for invasive fungal infections. This combination of factors has urged researchers to reconsider the continuing appropriateness of the current definitions.