Gilbert’s syndrome, also known as benign hyperbilirubinaemia, was described more than 100 years ago. It has usually been considered a physiological abnormality characterised by a mild elevation of the systemic level of unconjugated bilirubin, in the absence of any underlying liver or overt haemolytic disease. However, since the re-discovery of the potent antioxidant effects of bilirubin in the late 1980s, as well as multiple intracellular signalling pathways affected by bilirubin, an ever-increasing body of evidence suggests that individuals with Gilbert’s syndrome may benefit from the mild hyperbilirubinaemia and are actually protected from the development of a wide variety of “diseases of civilisation” such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases.