Plasticity of respiratory muscles must be considered in the context of their unique physiological demands. The continuous rhythmic activation of respiratory muscles makes them among the most active in the body. Respiratory muscles, especially the diaphragm, are non-weight-bearing, and thus, in contrast to limb muscles, are not exposed to gravitational effects. Perturbations in normal activation and load known to induce plasticity in limb muscles may not cause similar adaptations in respiratory muscles. In this review, we explore the structural and functional properties of the diaphragm muscle and their response to alterations in load and activity. Overall, relatively modest changes in diaphragm structural and functional properties occur in response to perturbations in load or activity. However, disruptions in the normal influence of phrenic innervation by frank denervation, tetrodotoxin nerve block and spinal hemisection, induce profound changes in the diaphragm, indicating the substantial trophic influence of phrenic motoneurons on diaphragm muscle.