Recent welcome efforts to define and agree objective criteria for cancer cachexia still raise many difficulties some of which are related to differences of opinion about the underlying causes of the cachexia syndrome. Much of the data on mechanisms of cachexia has been derived from rodent studies but there are many reasons why these experimental approaches are not as informative as expected in terms of understanding and correcting the clinical cancer cachexia syndrome. Indeed several different metabolic derangements have been described in animal and clinical studies but none have been proven to be universal. In response, a new generation of clinical trials of treatments for cachexia have reported or are underway which are based on very different mechanistic models. It remains to be seen whether any of these will find their place in the treatment of cancer cachexia and if so whether these interventions will lead to a more sophisticated understanding about the causes and subtypes of cachexia.