The part that genetics plays in the origin of Alzheimer's disease (AD) is a complex problem that is only now, in the last few years, beginning to be understood. Progress in the study of the epidemiology of AD, discovery of multiple AD loci, and interpreting how mutations affect and produce the AD phenotype have been the initial keys to unlocking the mysteries of this disease. We now know of the existence of at least three AD loci on chromosomes 14, 19, and 21 and are beginning to understand the role that one of these loci, APP, and its mutations plays in the progression of AD. On future studies using animal modeling and the positional cloning of the other AD loci, a definite model for AD should become evident within the next few years.