OBJECTIVE We review stable isotope tracer studies of apolipoprotein B-100 (apoB) kinetics concerning genetic polymorphisms and mutations that affect human lipoprotein metabolism. RESULTS In obese men, the allelic combination of the apoB signal peptide, SP24, and cholesteryl ester transfer protein, CETP B1B1, is independently associated with lower VLDL apoB secretion. Microsomal triglyceride transfer protein -493G/T carriers have reduced IDL apoB and LDL apoB production as compared with controls. Mutations in cholesterol transporters (ATP-binding cassette transporter G8 and Niemann-Pick C1 Like 1) are associated with reduced VLDL apoB secretion and increased LDL apoB production and catabolism. The ATP-binding cassette transporter G8 400K variant is a significant, independent predictor of VLDL apoB secretion. Mutations in lipases (lipoprotein lipase and hepatic lipase) and transfer proteins (lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein) alter their functional activity, which impact on VLDL and LDL kinetics. CONCLUSIONS Mutations in genes that regulate intrahepatic apoB assembly and lipid substrate availability to the liver impact on VLDL apoB secretion. Lipoprotein tracer studies can provide functional insight into the potential impact of genetic polymorphisms in regulating apoB metabolism in humans.