There has been much clinical and academic interest in the use of noninvasive positive-pressure ventilation (NPPV) in patients with acute and chronic respiratory failure. The use of NPPV in appropriately selected patients improves survival and decreases the need for endotracheal intubation. The most commonly used interfaces for NPPV are nasal masks or oronasal masks, but nasal pillows, mouthpieces, total face masks, and helmets can also be used. Critical care ventilators, portable volume ventilators, and ventilators designed specifically for NPPV can be used. There are three options for aerosol delivery during NPPV. The patient can be removed from NPPV and the aerosol administered by nebulizer or MDI in the standard manner, the aerosol can be delivered by nebulizer placed in-line between the circuit and the mask, or a spacer chamber can be placed between the circuit and the mask. There is presently no commercially available system designed specifically for aerosol delivery during NPPV with a bilevel (BiPAP) ventilator. However, in vitro and in vivo studies have demonstrated that a significant amount of bronchodilator can be administered by in-line nebulizer or MDI during NPPV. The evidence base for aerosol delivery during NPPV is not nearly as mature as the evidence for aerosol delivery during invasive mechanical ventilation. With NPVV, issues related to the optimal interface, ventilator settings, and aerosol generator (nebulizer versus MDI) are largely unexplored.