Human genetics has long been preoccupied with the study of simple, single locus traits and, indeed, it is still asserted that "the primary goal of human genetic analysis should be the detection and estimation of single gene effects" (102). But there is increased recognition that the greater portion of the human burden of disease and disability stems not from such conditions but rather those in which the appearance of the disorder is only the last stage in a lifelong train of prodromal states. There is almost universal agreement that our living conditions and behavior are major contributory factors to their occurrence. It is equally true that there are inherent differences among us which also contribute. The assessment of the roles of these contributors, intrinsic and extrinsic, and the development of environmental manipulations which cure or prevent disease and disability of this nature have become the new frontiers of genetics and human medicine. We have described briefly four investigative, genetic strategies, two essentially concerned with analysis and two with sampling, which can contribute to the conquest of these frontiers. We have attempted to place these strategies in an epidemiologic context.