Cachexia has a devastating impact on survival and quality of life for many cancer patients. A better understanding of the underlying mechanisms leading to the complex metabolic defects of cachexia, coupled with effective treatment options, will improve management of wasting in cancer patients. The growing appreciation that cancer cachexia results from the spillover effects of cytokine production by tumors on the integrated regulation of energy balance in different organs identifies potential therapeutic options. However, targeting such tumorkines requires a comprehensive understanding of their normal as well as pathophysiological functions, especially the crosstalk between inflammatory signaling and metabolic dysregulation. Recent advances in characterizing the surprising parallels between obesity and cancer cachexia provide new insights into these apparently divergent syndromes.