Releases of genetically manipulated mosquitoes have been conducted in numerous habitats with mosquito genera that transmit major human diseases. Since the 1950's Anopheles, Aedes and Culex spp. have been targeted by research intent on testing the feasibility of controlling these diseases by integrating genetic methods with conventional control options. Considering the challenges of altering reproductive capacity or implanting desirable features into feral mosquito populations, some of these attempts have been remarkably successful. But whether the goal has been to drive a genetic feature into a population or to suppress reproduction, a common barrier to success often has been the inability to produce mosquitoes that are competitive and exhibit normal behavioral fitness. With sterile Anopheles albimanus, the excellent fitness observed in field trials was subsequently diminished in mass-reared sterile males by the severity of the processes used to exclude females from the releases. However, this negative impact was overcome by development of genetic sexing methods. This accomplishment demonstrates the absolute need for emphasis on production of competitive stocks with which to implement vector control with genetically manipulated strains. With more robust insects such as screwworms and fruit flies, reductions in fitness may be overcome to some extent by increasing the ratios of released/feral populations. Such an approach might not be practical with the inherently less robust mosquito. Dealing with the fragility of mosquitoes poses unique challenges, but the An. albimanus experience focuses on the basic requirement for fitness among released stocks regardless of the genetic mechanism utilized.