The accurate determination of the types and amounts of bilirubin species in serum is important for diagnostic purposes as well as for therapeutic monitoring. However, of the determinations routinely performed in the clinical laboratory, those for bilirubins are not among the more accurate and exhibit significant method variability. In this review, the structural, stability, solubility, and albumin-binding properties of serum bilirubins are discussed with respect to their impact on analytical methods. Following a consideration of analytical standards, methods for the determination of unconjugated and conjugated bilirubins are reviewed and recent developments are evaluated. Finally, the present capabilities and future potential of the methods for producing information applicable to the development of new or improved methods of determination are summarized.