Hypobetalipoproteinemia is an autosomal codominant disorder characterized by decreased or absent plasma concentrations of the apolipoprotein (apo) B-containing lipoproteins. Heterozygotes for hypobetalipoproteinemia typically have plasma concentrations of apoB and low density lipoprotein (LDL)-cholesterol that are one-fourth to one-half normal and are usually clinically asymptomatic. In the homozygous state, however, apoB and LDL-cholesterol levels are extremely low or undetectable. When the@-lipoproteins are absent, the clinical phenotype can be severe and may include fat malabsorption, acanthocytosis, retinitis pigmentosa, and neuromuscular degeneration. This severe phenotype observed in some cases of homozygous hypobetalipoproteinemia is indistinguishable from that of abetalipoproteinemia, a recessively inherited apoB deficiency state (1, 2). Obligate heterozygotes for abetalipoproteinemia have normal plasma lipid and lipoprotein levels, in contrast to familial hypobetalipoproteinemia heterozygotes. During the past 5 years, our understanding of hypobetalipoproteinemia has been enhanced by the description of many different apoB gene mutations that cause hypobetalipoproteinemia. In this review, we summarize the recent progress in the molecular genetics of hypobetalipoproteinemia. We also review the history of hypobetalipoproteinemia, which has, to an extent, been lost amid the excitement of delineating the responsible apoB gene mutations. Finally, we summarize the current understanding of the metabolic abnormalities and the clinical consequences of hypobetalipoproteinemia.