Inheritance of the apolipoprotein E (APOE = gene; apoE = protein) epsilon 4 gene is associated with a higher risk for development of Alzheimer's disease (AD) and for occurrence of this illness at a younger age. APOE gene dose and genotype interact with gender, ethnicity, and age to influence the probability of developing AD, as well as the rate of disease progression. The sensitivity and specificity of APOE genotyping, however, and the longer-term implications of the epsilon 4 allele as a susceptibility factor for AD, are not yet adequately understood to recommend the use of APOE genotyping in genetic counseling of asymptomatic family members of AD patients. Insufficient evidence also exists at this time to recommend APOE genotyping as an adjuvant for the differential diagnosis of dementia or as a possible predictor for response to drug therapy. These potential future clinical indications for apoE genotyping are under active investigation.