Apolipoprotein E (apoE) is one of several lipoprotein transfer genes. A primary function of this protein is the mediation of receptor-mediated lipoprotein removal from the blood. Several studies have demonstrated that genetic variation at the apoE locus is associated with an increased risk of developing atherosclerosis, and recent studies implicate this same genetic variation in determining susceptibility to Alzheimer's disease. An apoE-deficient mouse has been created to further understand the role of apoE in these areas. This review briefly discussed the biological and clinical importance of this protein and describes the early experiments performed in the apoE-deficient mouse.