The poloxamer 407 (P-407) nongenetic, nondiet–induced mouse model of dose-controlled hyperlipidemia and atherosclerosis was first introduced in 1992. Dyslipidemia is produced in C57BL/6 mice of either sex after intraperitoneal administration of P-407 that is a polyether-based nonionic surface active agent. Aortic atherosclerotic lesions begin to form after 1 month of repeated P-407 administration and obtain maximum size, numerical density, and human-like pathological features by 4 months. Our laboratory published a review of this model in 2004, although an update would seem both appropriate and timely based on new findings since 2004. Using P-407–treated mice, we have investigated the effect that hyperlipidemia has on the activity of several classes of proteases in the heart, liver, and serum; extensively characterized lipoprotein fractions and subfractions associated with atherogenic plasma lipids; investigated whether several key vascular cell adhesion molecules were perturbed; and determined whether the biological activity of 2 peroxisome proliferator–activated receptors was modulated both in vitro and in vivo. Based on our findings since 2004, as well as those before 2004 (1992–2004), we would strongly suggest that the P-407–induced hyperlipidemic mouse model represents a convenient, inexpensive, and well-documented alternative mouse model with which to study cardiovascular heart disease arising from dyslipidemia and atherosclerosis.