The concept that an insect species' genome could be altered in a manner that would result in the control of that species (i.e., autocidal control) or in the replacement of a pestiferous strain of the species with a more benign genotype was first proposed in the mid-twentieth century. A major research effort in population genetics and ecology followed and led to the development of a set of classical genetic control approaches that included use of sterile males, conditional lethal genes, translocations, compound chromosomes, and microbe-mediated infertility. Although there have been a number of major successes in application of classical genetic control, research in this area has declined in the past 20 years for technical and societal reasons. Recent advances in molecular biology and transgenesis research have renewed interest in genetically based control methods because these advances may remove some major technical problems that have constrained effective genetic manipulation of pest species. Population genetic analyses suggest that transgenic manipulations may enable development of strains that would be 10 to over 100 times more efficient than strains developed by classical methods. Some of the proposed molecular approaches to genetic control involve modifications of classical approaches such as conditional lethality, whereas others are novel. Experience from the classical era of genetic control research indicates that the population structure and population dynamics of the target population will determine which, if any, genetic control approaches would be appropriate for addressing a specific problem. As such, there continues to be a need for ongoing communication between scientists who are developing strains and those who study the native pest populations.