Bed-rest, of only a few days, reduces muscle protein synthesis and causes skeletal muscle atrophy, as well as reducing insulin sensitivity. However, the magnitude and trajectory of these responses have not been investigated concurrently, such that the metabolic adaptations to acute (days) vs chronic (months) bed-rest are unclear, particularly as published research studies have been confounded by volunteers being in positive energy balance. Moreover, the impact of post bed-rest ambulation versus exercise-supplemented remobilisation on muscle volume, muscle protein synthesis and insulin-stimulated glucose uptake is also unclear. Bed-rest is not associated with increased inflammatory burden, however in musculoskeletal trauma, where significant muscle mass loss and insulin resistance also occurs, systemic and muscle inflammation prevail alongside immobilisation. Importantly, the relative impact of inflammation vs immobilisation on muscle mass loss and the underlying mechanisms involved are unresolved. This talk will explore the mechanisms of immobilisation and trauma-induced muscle mass loss and insulin resistance and discuss current gaps in our understanding as well as directions for future research. This information has important implications in various clinical applications such as short duration hospitalisation, injury and recovery.