Purpose of review Wasting diseases are characterized by progressive deterioration of nutritional status that negatively influences patients' outcome. The better understanding of the pathogenic mechanisms of wasting may lead to effective therapies. Tryptophan metabolism has unique features suggesting a critical role in influencing human metabolism under normal and pathological conditions. Recent findings During disease, inflammatory response favours the local depletion of the essential amino acid tryptophan, thereby inhibiting cellular proliferation. Tryptophan depletion may also mediate immunotolerance to foreign antigens. In contrast, brain accumulation of tryptophan contributes to wasting by increasing oxidative stress and hypothalamic serotonin neurotransmission, and thereby triggering the onset of sickness behaviour followed by depressive-like behaviour. Summary Tryptophan metabolism is critical in mediating a number of important biological responses. Restoring tryptophan metabolism may well result in enhanced recovery from disease.