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Despite multiple protocols for the prevention of ventilator-associated pneumonia (VAP), respiratory infections have not been eliminated in the ICU. The profound disruption in both airway integrity and mucociliary clearance caused by the endotracheal tube makes it unlikely there will ever be a zero rate of respiratory infection in critically ill ventilated patients or a 100% cure rate when infection is present. In fact, options for treatment are diminishing as bacteria resistant to most, or in some hospitals all, systemic antibiotics increase in prevalence from our liberal use of systemic antibiotics. Inhaled therapy with proper delivery will result in the high concentrations of antibiotics needed in the treatment of increasingly resistant organisms.Data from many recent investigations have focused on inhaled antibiotics as: adjunctive therapy to systemic antibiotic for VAP, monotherapy for VAP, and as monotherapy for ventilator-associated tracheobronchitis. The clinical outcomes of these studies will be reviewed as well as their effect on multidrug-resistant organisms.The present review will focus on the rationale for inhaled therapy, the current studies examining the delivery and clinical efficacy of inhaled antibiotics, and the potential role for this mode of delivery actually decreasing antibiotic resistance in the respiratory tract.