Apolipoprotein E is a polymorphic glycoprotein in humans with a molecular mass of 34.5 kDa. It is a component of chylomicron remnants, very low density lipoprotein, low density lipoprotein and high density lipoprotein, and is primarily responsible for maintaining plasma lipid homeostasis. In addition to these well-documented functions, recent studies in experimental mouse models, as well as population studies, show that apolipoprotein E also plays an important role in the development of obesity and insulin resistance. It is widely accepted that disruption in homeostasis between food intake and energy expenditure, and the subsequent deposition of excess fatty acids into fat cells in the form of triglycerides, leads to the development of obesity. Despite the pivotal role of obesity and dyslipidemia in the development of the metabolic syndrome and heart disease, the functional interactions between adipose tissue and components of the lipoprotein transport system have not yet been investigated thoroughly. In this minireview, we focus on the current literature pertinent to the involvement of apolipoprotein E in the development of pathologies associated with the metabolic syndrome.