For both lung and systemic diseases, aerosol delivery of drugs into the lungs can often offer substantial advantages over other routes of administration. In the intensive care unit, however, the artificial airway can be a substantial barrier to aerosol delivery, so clinicians must pay careful attention to the ventilator pattern, the delivery gas humidity/density, the device characteristics, and the circuit/tube properties. When those are optimized, aerosol delivery from a nebulizer or metered-dose inhaler and through an endotracheal tube can begin to approach that seen in a nonintubated patient. Novel approaches, such as generating the aerosol within the airway, offer the opportunity to greatly increase deposition efficiency and focal drug targeting in intubated patients.