This chapter discusses some of the general concepts of kinetic analysis and mathematical modeling that are relevant to studies that have employed labeled bilirubin and some of the more important examples of the application of these techniques to studies of bilirubin metabolism. The first involves extending the standard protocol for defining the disappearance from plasma of intravenously administered radiolabeled unconjugated bilirubin by counting radioactivity in the upper polar layers of the Weber-Schalm partition of plasma samples. The second study involves the use of preparations of radiolabeled conjugated bilirubin to study the kinetics of the conjugated pigment in vivo in experiments having similar designs to analogous studies using radiolabeled unconjugated bilirubin. Finally, a distributed modeling approach should be incorporated into the experimental design and analysis of future tracer studies of bilirubin metabolism in vivo if insights into gradients of concentration of unconjugated and conjugated bilirubin from the portal to the centri-lobular zone of the hepatic lobule are to be obtained.