Much evidence supports the use of non-invasive ventilation (NIV) in patients who have acute and chronic respiratory failure and aerosolized medications are increasingly used in this patient population. Successful application of aerosol therapy during NIV depends on the effectiveness of the drug deposition in the lungs. Previous evidence showed that many factors impact aerosol delivery to patients receiving NIV. Those factors include mode of ventilation, ventilator parameters, type of ventilator circuit, the position of the aerosol device, the location of leak port, type of exhalation valve, humidity, enhanced condensational growth, type of aerosol device, and interface as well as delivery technique. The purpose of this paper is to review the available evidence related to aerosol therapy during NIV and provide recommendations to optimize aerosol drug delivery to patients receiving NIV.