To illuminate modern ideas about Gilbert's syndrome (GS). GS is a common familial hyperbilirubinemia that can reduce the risk of various age-related diseases due to the antioxidant properties of bilirubin. In this case, slightly elevated unconjugated bilirubin in GS is strongly associated with a "reduced" prevalence of chronic diseases, in particular cardiovascular disease (CVD), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic byproduct of heme catabolism, and emphasize the importance of understanding its potential beneficial physiological and harmful pathophysiological effects. With this information, we hope to improve understanding of bilirubin metabolic disorders, highlight the diagnostic importance of these conditions, and map out the potential impact of GS on disease resistance.