Noninvasive mechanical ventilation (NIV) has become a standard of care in select patients with both hypercapnic and non-hypercapnic acute respiratory failure (ARF). Consequent to the increasing use of NIV, new interfaces of different designs, shapes, sizes, and materials have been proposed for clinical use in recent years. The aim of this report is to examine the most relevant physiological aspects related to the choice of interface with particular emphasis on the problems related to dead space and air leaks that may affect the synchrony between the patient and the machine, ultimately determining the patient's compliance and therefore NIV success.