Given the continuing difficulty of identifying genes for complex disorders in a robust, replicable manner, and the extensive resources devoted to this effort, it is becoming increasingly important to analyze the relative benefits of genomics research for public health applications and for the understanding of disease pathogenesis. To establish priorities for genetics research, we review and evaluate several characteristics of selected exemplary complex diseases, including phenotypic accuracy, knowledge of specific and nonspecific genetic and environmental risk factors, and population prevalence and impact. We propose that complex diseases with the strongest evidence for genetic etiology, limited ability to modify exposure or risk factors, and high public health impact should have the highest priority for genetics research.