Hypercholesterolaemia is a well-defined risk factor for both morbidity and mortality in coronary artery disease. However, in chronic heart failure high levels of plasma cholesterol have been associated with better survival. The reason for this inverse epidemiology is potentially explained by the ability of plasma lipoproteins to bind and detoxify bacterial lipopolysaccharide (LPS, endotoxin), a cell-wall component of Gram-negative bacteria. This hypothesis has been termed the “endotoxin-lipoprotein hypothesis”, first published in 2000. LPS is one of the strongest inducers of pro-inflammatory cytokine release in heart failure. This article summarises the known pathophysiology of increased endotoxin concentrations entering the blood stream via the hypoperfused oedematous bowel wall. Furthermore, it discusses technical problems with the measurement of LPS, and reviews its signalling cascade and the biological effects of LPS as well as the potentially protective ability of serum lipoproteins in chronic heart failure.