Loss of skeletal muscle is the main feature of cachexia that predicts risk of physical impairment, post-operative complications, chemotherapy toxicity, and mortality in patients with cancer. Studies in animal models provide evidence in principle that such muscle loss and these risks can be reversed. In the experimental setting cancer-associated muscle loss has been shown to have distinct pathophysiology involving specific catabolic pro-inflammatory signals (such as MIC-1/Growth and Differentiation Factor (GDF)-15, Interleukin-6, eicosanoids), tumor derived catabolic actors (e.g. parathyroid hormone related peptide, PTHrP) and antiproliferative factors (e.g.myostatin) or loss/reduced activity of anabolic effectors (e.g. androgens). Muscle loss can be prevented as well as reversed after it is already well established, by agents targeting these signals in experimental systems. A key finding is that the muscle wasting can be dissociated from the progression of the cancer itself. Zhou et al [1]provide one example:l the activin IIB receptor (ActRIIB) mediates antiproliferative and catabolic effects on muscle by myostatin and Activin and pharmacological blockade of these actions by a decoy receptor resulted in muscle hypertrophy, enhanced strength, and extended survival. Tumor growth and tumor-associated inflammation were not affected by this treatment, suggesting that the extension of survival was associated with the specific gain of muscle mass . Such findings define the rationale for placing muscle as the therapeutic target and gain of muscle mass as the first primary outcome of new cachexia treatments currently in clinical trials. In moving forward with clinical trials in this area, a central question is whether patients with advanced cancer possess the anabolic potential for reversal of muscle wasting as has been shown repeatedly in animal models. Od age, poor nutritional status, deconditioning, inflammation, cancer, and comorbid conditions are features of the patients typically affected by cancer, making this clinical entitly considerably more complex than the controlled animal models. Patients with cancer are typically older (the median age of diganosis is 65 y) and prone to lose muscle mass and function rapidly during periods of inactivity. Further catabolic losses of muscle are induced by many types of cancer therapy either because they cause malnutrition or because of their mechanisms of action to inhibit proliferation and anabolism which is directed at the tumor but may occur off-target in the muscle. The constrainted mentioned above notwithstanding, several findings support the suggestion that clinically significant gains in muscle mass are possible in patients with cancer. Recent reports demonstrate quantitiatively significant lean tissue / muscle mass gains in patients with advanced cancer receiving anticachexia therapeutics. Some recently published findings include results of phase 2 trials of anamorelin (an orally bioavailable, small-molecule ghrelin mimetic with appetite-stimulating and anabolic activities) [2]. This agent stimulates the growth hormone secretagogue receptor centrally, mimicking the appetite-stimulating and growth hormone-releasing effects of ghrelin. A phase 2 study of the orally active selective androgen receptor modulator enobosarm induced gain of lean body mass of median 1·5 kg (range −2·1 to 12·6, p=0·0012) in a group patients of various cancers, whereas the placebo-treated group lost lean mass [3]. In a phase 2 study of patients with cholangiocarcinoma,selumetinib, a MEK kinase inhibitor (associated with systemic reduction in interleukin-6 levels) induced gain of skeletal muscle detected by CT scans [4]. The mean overall gain of total lumbar muscle cross-sectional area was 13·6 cm2 (SD 11·9; or ∼2·3 kg of muscle on a whole-body basis). Muscle protein synthesis is clearly not shut down in patients with cancer. Several studies suggest that protein synthesis in muscle is unimpaired and responsive to the systemic availability of amino acids, albeit a somewhat higher quantity than in young and healthy individuals [5] Future priorities in therapetic interventions for cancer associated muscle loss include matching of the most highly specific mechanism-based therapeutics to those patients likely to most benefit and the otimization of the muscle anabolism by the strategic combination of anti-catabolic and andbolic modalities of treatment, aligned with nutrient mixtures with levels and proprtions of amino acids and other nutrients essentailfor muscle anabolism.