Neuromuscular respiratory failure can result from any disease that causes weakness of bulbar and/or respiratory muscles. Once compensatory mechanisms are overwhelmed, hypoxemic and hypercapnic respiratory failure ensues. The diagnosis of neuromuscular respiratory failure is primarily clinical, but arterial blood gases, bedside spirometry, and diaphragmatic ultrasonography can help in early assessment. Intensive care unit (ICU) admission is indicated for patients with severe bulbar weakness or rapidly progressing appendicular weakness. Intubation should be performed electively, particularly in patients with dysautonomia. Patients with an underlying treatable cause have the potential to regain functional independence with meticulous ICU care.