Neuromuscular diseases (NMD) can affect all major respiratory muscles, leading to the development of respiratory failure, which is the most common cause of morbidity and mortality in patients affected by those conditions. Based on the clinical onset of acute respiratory failure (ARF), NMD can be classified into two main categories: 1) slowly progressive NMD with acute exacerbations of chronic respiratory failure, and 2) rapidly progressive NMD with acute episodes of respiratory failure. The most common slowly progressive NMDs, such as motor neuron diseases and inherited myopathies, account for the majority of NMD patients developing chronic neuromuscular respiratory failure at risk of acute exacerbations. Conversely, rapidly progressive NMDs, such as Guillain-Barré syndrome and myasthenic crises, are characterized by a sudden onset of ARF, usually in patients with previously normal respiratory function. The patho-physiological mechanisms responsible for ARF in NMD and the variety and complexity of specific challenges presented by the two main categories of NMD will be analyzed in this review, with the aim of providing clinically relevant suggestions for adequate respiratory management of these patients.