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Weight and appetite loss in cancer patients, referred to as the cancer anorexia-cachexia syndrome, is a complex, multifactorial syndrome, defined by an ongoing loss of skeletal muscle mass, with or without loss of fat mass, which cannot be fully reversed by conventional nutritional support, and may lead to progressive functional impairment. It is a hypercatabolic state in the context of chronic inflammatory response best described in the setting of cancer but can also be seen in other advanced chronic illness. Cancer cachexia occurs in approximately 50% of cancer patients, and in 80% of those with advanced cancer. It impacts adversely on function, treatment tolerability and treatment response, and health service utilization, but most importantly, dignity, sense of self, quality of life, and survival. The pathophysiology of cancer cachexia is complex and multifactorial. It is characterized by a negative protein and energy balance, driven by a variable combination of reduced food intake, increased resting energy expenditure, and net loss of lean tissue. The best approach to weight and appetite loss among cancer patients is a multimodal therapy, in which a personalized combination of pharmacologic and nonpharmacologic treatments is implemented. This chapter will provide an overview of the cancer anorexia cachexia syndrome as relevant to the practice of clinicians of all disciplines managing cancer patients.