Among the devices employed for aerosol generation (metered-dose inhalers, nebulizers, and dry powder inhalers) only metered-dose inhalers and nebulizers are routinely employed for aerosol delivery to mechanically ventilated patients. The ventilator circuit and artificial airway were previously thought to be major barriers to effective aerosol delivery to mechanically ventilated patients. In the past decade in vitro and in vivo investigations have contributed to a better understanding of the complex array of factors that influence inhaled drug delivery in mechanically-ventilated patients. Several investigators have shown that with careful attention to the administration technique aerosol delivery efficiency in mechanically-ventilated patients is comparable to that in ambulatory patients. The ability to efficiently deliver aerosols should lead to wider clinical application of inhaled therapies in patients receiving mechanical ventilation.