Invasive mycoses have emerged as a major cause of morbidity and mortality. Epidemiological studies have shown that surgery services have the highest rate of Candida infections in the hospital. In addition to classical risk factors, heavy Candida colonization, recurrent gastrointestinal perforations, and acute pancreatitis are frequently associated with invasive candidiasis. Because prompt initiation of antifungal therapy is critical for cure but difficult to accomplish, prevention of fungal infections may play an important role in this clinical setting; however, few prophylactic or preemptive studies have been done to date. The choice, route of administration, and dose of the antifungal and comparator regimens and the use of clinically relevant and robust study end points are critical for the trial design. Various criteria have been used to identify patients at risk of candidiasis: surgical condition, presence of multiple risk factors, colonization indexes, or expected length of stay in the intensive care unit. Some are not selective enough, and others are time consuming and expensive. Rigorous selection of high-risk patients is crucial to optimize the risk-benefit ratio of preventive antifungal strategies. The aim is to maximize chances of reducing morbidity and mortality while minimizing treatment costs, exposure of low-risk patients to adverse events, and emergence of resistant fungal strains.