Although the verdict may still be out on the clinical utility of prophylactic administration of amphotericin B, the findings presented by Marra et al. strengthen the argument for its theoretical use by demonstrating that a relatively reproducible range of concentrations can be achieved in the target patient group. Additionally, it was demonstrated that at an inhaled dose of 30 mg, amphotericin B concentrations at the interface of epithelial lining fluid and the lung tissue, the battleground for host invasion, approach therapeutically relevant concentrations. Even though the debate over the utility of aerosolized administration of antimicrobials is far from over, data continue to accumulate that demonstrate the tolerability and describe the characteristics of drug distribution of nebulized amphotericin B. Even with the absence of definitive clinical data, aerosolized administration of amphotericin B may become a viable option for prophylaxis against serious pulmonary fungal infections owing to the severity of disease, lack of serious toxicities associated with this route of administration, and pharmacokinetic and susceptibility data, suggesting a theoretical basis for activity.