Fluconazole is currently a first-line agent used for therapy of non-critically ill patients with candidal infection. Its efficacy, the availability of an oral formula, and its relatively low toxicity make it a very attractive drug for use in many clinical situations. The advisability of prophylaxis and empirical treatment in transplant patients is a difficult issue for the following reasons: the potential emergence of resistance to the azoles, the lack of solid data establishing its advantage over placebo and/or oral nonabsorbable antifungal agents in some of the clinical conditions encountered, its ineffectiveness against molds, and its cost. Judicious use of fluconazole where its efficacy has been well established would provide the best therapy for patients and would limit the emergence of potential pathogens. As new antifungal agents are approved for clinical use, appropriate clinical trials will need to be designed and conducted in order for clinicians to make rational decisions in selecting the most appropriate drug for the specific indication. Prophylaxis and treatment with fluconazole in various transplant situations is reviewed.