Chronic heart failure (CHF) remains an important and increasing public health care problem. Not until recently it has been recognised that CHF is a chronic progressive disorder affecting different physiological and metabolic pathways. Nowadays CHF is reviewed as the consequence of an interplay of haemodynamic, neurohormonal, immunological, and endocrine mechanisms, initially thought to have beneficial adaptive effects for the organism to compensate the heart's inability to pump properly. However, these secondary changes eventually contribute to further deterioration of CHF. This review focuses on metabolic features observed in patients with CHF and discusses immunological and neuroendocrine aspects and their potential contribution to the pathogenesis of CHF. The overall evidence suggests that advanced CHF is a multifactorial metabolic syndrome that can lead to cardiac cachexia and then carries a very poor prognosis. Joint efforts of cardiologists, endocrinologists, and immunologists are required to develop therapeutic strategies able to improve the metabolic status of CHF patients.