The overexpression of proteins as transgenes or by adenovirus-mediated gene transfer as well as the disruption of genes by homologous DNA recombination in the mouse provide powerful tools to dissect the role of individual proteins in complex biological pathways. These and similar techniques have been widely used to characterize the function of most of the players involved in lipoprotein metabolism. These models are expected to greatly advance the finding of new therapeutic strategies for the treatment of disorders of lipoprotein metabolism.