Neurologists are often called to evaluate patients with both defined and undiagnosed neuromuscular disorders when respiratory failure develops to determine if there is a neuromuscular cause. Being able to confidently diagnose neuromuscular respiratory failure and intervene appropriately is imperative, as early intervention and determination of the cause have survival implications. Outcomes are poor when the cause of neuromuscular weakness and resultant respiratory failure cannot be identified. This review discusses the clinical recognition of primary neuromuscular respiratory failure, its pathophysiology, diagnostic evaluation, and management, focusing on management of respiratory failure in the setting of Guillain-Barré syndrome and myasthenic crisis.