Cachexia is a wasting condition associated with late stages of many chronic illnesses and may be present in up to 80% of patients with advanced cancers. Cachexia is a metabolic derangement resulting in a disturbance to the homeostasis of muscle breakdown and synthesis, favoring catabolism and muscle loss. Despite making strides in treating cancer itself, there have been no major advances in the treatment of cachexia pharmacologically or nutritionally. Clinical trials using anti-TNF biologics and thalidomide have largely failed. A new approach may be to focus on other possible waste-inducing mediators, possibly derived from mast cells, and the beneficial action of select natural flavonoids.