Lipoprotein tracer kinetics studies have for many years provided new and important knowledge of the metabolism of lipoproteins. Our understanding of kinetics defects in lipoprotein metabolism has resulted from the use of tracer kinetics studies and mathematical modeling. This review discusses all aspects of the performance of kinetics studies, including the development of hypotheses, experimental design, statistical considerations, tracer administration and sampling schedule, and the development of compartmental models for the interpretation of tracer data. In addition to providing insight into new metabolic pathways, such models provide quantitative information on the effect of interventions on lipoprotein metabolism. Compartment models are useful tools to describe experimental data but can also be used to aid in experimental design and hypothesis generation. The SAAM II program provides an easy-to-use interface with which to develop and test compartmental models against experimental models. The development of a model requires that certain checks be performed to ensure that the model describes the experimental data and that the model parameters can be estimated with precision. In addition to methodologic aspects, several compartment models of apoprotein and lipid metabolism are reviewed.