Antifungal prophylaxis is regularly used during treatment of patients with some cancers, as subgroups with high rates of invasive fungal infections are readily identified; for these patients, prophylaxis has been shown to be of value. High-risk liver transplant recipients also benefit from antifungal prophylaxis. Although the idea of extending this concept to the prevention of candidal infections in the larger population of critically ill patients who are seen in the intensive care unit (ICU) and who do not have neutropenia is attractive, implementation of this strategy is difficult because of the widely varying characteristics of patients in the ICU. Two studies have shown the benefit of such prophylaxis, but the benefit was shown only in selected groups of patients who had an unusually high risk for invasive candidiasis. Although the concept is sound, broad-scale implementation of antifungal prophylaxis would be premature and costly, both financially and with regard to resistance and toxicity. Investigations are needed to define and prove the utility of predictive tools for the identification of patients in the ICU who would benefit from prophylaxis.