Medication delivery into the lungs can be used to provide a high therapeutic index for agents targeted to specific lung diseases. In addition, the lung can be used as a portal of entry for other agents targeted to systemic diseases. Delivery of medications into the lung can be accomplished by either instillation or aerosolization. Instillation approaches are limited by the fluid volume that can be given safely, and instilled liquids distribute according to gravity. In contrast, aerosolization approaches can deliver larger volumes over longer periods and aerosols distribute according to ventilation. In the mechanically ventilated patient, externally generated aerosols have very poor lung delivery because the endotracheal tube functions as a barrier to aerosol passage. Novel aerosol generating systems at the ends of small-diameter catheters that can be placed into the trachea (or beyond) are being developed to address this. In vitro testing has shown these systems to be capable of producing appropriately sized particles, with high rates of lung deposition. These catheters could be coupled with tracheal gas insufflation systems, not only to deliver therapeutic aerosols but also to create water aerosols to supply necessary humidification during tracheal gas insufflation.