In selected patients, noninvasive positive pressure ventilation (NIPPV) with a facemask is now commonly employed as the first choice for providing mechanical ventilation in the intensive care unit (ICU). Aerosol therapy for treatment of acute or acute-on-chronic respiratory failure in this setting may be delivered by pressurized metered-dose inhaler (pMDI) with a chamber spacer and facemask or nebulizer and facemask. This article reviews the host of factors influencing aerosol delivery with these devices during NIPPV. These factors include (1) the type of ventilator, (2) mode of ventilation, (3) circuit conditions, (4) type of interface, (5) type of aerosol generator, (6) drug-related factors, (7) breathing parameters, and (8) patient-related factors. Despite the impediments to efficient aerosol delivery because of continuous gas flow, high inspiratory flow rates, air leaks, circuit humidity, and patient-ventilator asynchrony, significant therapeutic effects are achieved after inhaled bronchodilator administration to patients with asthma and chronic obstructive pulmonary disease. Similarly to invasive mechanical ventilation, careful attention to the technique of drug administration is required to optimize therapeutic effects of inhaled therapies during NIPPV. Assessment of the patient's ability to tolerate a facemask, the level of respiratory distress, hemodynamic status, and synchronization of aerosol generation with inspiratory airflow are important factors contributing to the success of aerosol delivery during NIPPV. Further research into novel delivery methods, such as the use of NIPPV with nasal cannulae, could enhance the efficiency, ease of use, and reproducibility of inhalation therapy during noninvasive ventilation.