OBJECTIVES: Bilirubin (BR), a protective endogenous antioxidant is cytotoxic at high concentrations. Its intracellular levels are regulated by a system comprising haem oxygenase, biliverdin reductase and CYP2A5 enzymes, and considered  to be a molecule that promote health in adults. This paper will highlight the association between bilirubin and pathological conditions such as CVD, cancer, diabetes and neurodegenerative diseases. Furthermore, the mechanism by which bilirubin and its metabolism may influence disease prevention, will also be discussed. METHODS: Studies  on serum bilirubin levels and association with prevalence and incidence of oxidative stress related chronic disease, as well as experimental studies were collated and reviewed. RESULTS: Mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic disease especially CVD, cancer and metabolic diseases.It has been suggested as a biomarker and predictor of these diseases. Experimental studies indicate that it is a strong endogenous antioxidant and tumour suppressor agent, which would confer this protective properties. CONCLUSIONS: BR is promising molecule which importance should be considered in clinical practice. However, greater molecular work is needed to strengthen this conclusion.