Cachexia is considered as a complex metabolic disease accompanied by systemic inflammation. However, we still do not understand the essential nature of the metabolic disorder associated with cachexia or the precise molecular mechanisms that drive cachexia. This reviewsummarizes the current knowledge on the pathogenesis of cancer cachexia obtained mainly from mouse models with emphasis on the findings that could reach the bedside in the future. Basic studies using animal models of cancer cachexia indicate that mediators such as pro-inflammatory cytokines and members of TGF-b superfamily disturb the cross-talks among metabolism-related organs including skeletal muscle, adipose tissue, liver, and CNS and thereby induce the collapse of metabolic homeostasis. The inhibitors of these mediators are currently under development for the treatment of cancer cachexia. Skeletal muscle atrophy is a key feature of cancer cachexia and is induced by enhanced proteolysis via ubiquitin-proteasome system and autophagy-lysosome system, as well as by decreased protein synthesis and increased fatty acid oxidation. Adipose tissue atrophy due to excessive lipolysis is another common feature of cancer cachexia, and the involvement of the browning of white adipose tissue and of the increased energy expenditure associated with the futile cycle of lipolysis/lipogenesis is suggested. The liver of cachectic tumor-bearing mice shows increased gluconeogenesis which leads to energy expenditure via futile cycle, and also develops steatosis due to decreased triglyceride usage. In the CNS, inflammation in the hypothalamus induces anorexia and excessive peripheral energy expenditure. Cachectic animals also showresistance to the appetite-promoting effects of ghrelin. We hope that cancer cachexia will gain better awareness in the near future, leading to the growth and progress of the research field, and that the elucidation of its pathogenesis will contribute to the development of novel preventive/therapeutics strategies.