Muscle atrophy is a phenotypic trait of immobilisation and increased inflammatory burden, but it is unlikely that common cellular and molecular mechanisms prevail between the two. The suppression of muscle protein synthesis seems to be the primary driver of muscle mass loss in human immobilisation (De Boer et al., 2007), and that includes blunting of post-prandial increases in muscle protein synthesis (anabolic resistance, Glover et al., 2008). However, there is a substantial gap in the understanding of the mechanistic drivers of this physiological adaptation. The heightened inflammatory states of sepsis and trauma are associated with major and rapid changes in muscle protein turnover and mass in both rodents and humans, which is thought to reflect the suppression of muscle anabolic signalling (Lang et al., 2007), and activation of several pathways important to muscle protein breakdown, including ubiquitin-proteasome pathway, calpain- and lysosome-dependent proteolytic pathways (Voisin et al., 1996). Evidence points to Akt (protein kinase B) signaling and FOXO transcription factors forming part of a common signaling pathway regulating both muscle protein synthesis and breakdown in this scenario (Crossland et al., 2008). However, whilst tracer based measures of protein turnover in the post-absorptive state confirm that lipopolysaccharides (LPS) infusion decreases muscle (rat) and leg (human) protein synthesis, this appears to be balanced by a decrease in leg breakdown in humans (Vesali et al., 2009). Importantly, given muscle protein synthesis is accepted to be low in the post-absorptive state, it would appear that accelerated muscle wasting in sepsis is most likely attributable muscle cytokine mediated inhibition of nutrient mediated increases in muscle protein synthesis, i.e. LPS infusion induces profound muscle anabolic resistance to nutrition in humans. Given muscle atrophy is an important clinical consequence of sepsis and trauma that impacts negatively on patient survival and recovery, suppression of muscle pro-inflammatory cytokine status may prove beneficial under these conditions.