Noninvasive ventilatory support (NVS) is sometimes reported as suboptimal in patients with neuromuscular disease (NMD). The reasons for this include inadequate ventilator settings and/or lack of interface tolerance. NVS has been used for many years in patients with NMD disorders as a viable alternative to continuous ventilatory support via a tracheostomy tube. The mouthpiece ventilation (MPV) is a ventilatory mode that is used as daytime ventilatory support in combination with other ventilatory modalities and interfaces for nocturnal NVS. However, there is still a poor understanding of this method’s benefits compared with other modalities. This review aims to highlight the indications and advantages along with the disadvantages of MPV.