Conjugated linoleic acid (CLA) inhibits carcinogenesis and atherosclerotic plaque formation and delays the onset of diabetes in experimental animals. Whereas a plethora of data has demonstrated beneficial effects in rodent models, little work has been done to determine the role of dietary CLA in human health. The ability of CLA to modulate lipid metabolism appears to be a pivotal mechanism of CLA's beneficial effects in mice and rats. In particular, dietary CLA induces the expression of genes dependent in part on the transcription factor, peroxisome proliferator-activated receptor (PPAR). Furthermore, several CLA isomers are high-affinity ligands and activators for PPAR alpha. Within various rodent species and strains, dietary CLA exerts varying potencies; therefore, the differences in species' sensitivities are of great importance when trying to extrapolate the rodent data to be relevant in humans. This review presents the latest findings of the ability of CLA to alter lipid metabolism and gene expression in several different strains of mice and rats and speculates on the implications of these findings for human health.