Transgenic mouse models have been crucial to our current understanding of the mechanisms of lipoprotein metabolism. Moreover, these models have greatly advanced our understanding of the pathology associated with altered lipoprotein levels. Recent progress has been made in cellular uptake, intracellular metabolism, cellular efflux mechanisms and transcriptional regulation. In particular, much progress has been made in our understanding of events that take place in the vessel wall. In addition, the transgenic mouse model is becoming a crucial tool in genomic studies to evaluate gene function, as well as a subject of genome-wide expression studies. The present review describes progress in all of these areas and shows that animal models are likely to remain important to our view of gene function in the context of the whole organism.