When respiratory muscle demands for energy exceed supplies, the energy stored within the muscles is depleted and the force of contraction diminishes. This state is called inspiratory muscle fatigue. When it occurs alveolar ventilation decreases, arterial carbon dioxide tension (PaCO2) increases and hypercapnic respiratory failure ensues. It has also been suggested that such a dysfunction of the respiratory muscles contributes to the pathogenesis of acute respiratory failure. The purpose of this article is to review those factors that predispose to respiratory muscle fatigue and determine energy demand and supply and the principal means of investigation available to detect respiratory muscle fatigue in the clinical setting.