Mice have become the model of choice for studies of Down syndrome due to the fact that mouse chromosome 16 bears a striking resemblance to human chromosome 21. This has allowed researchers to create various mouse models of Down syndrome, but this is a tricky business on many levels. Great expertise is required to manipulate DNA to create these original "engineered" mice, and many attempts fail to produce animals that survive, breed, or have the characteristics typical of a mouse version of Down syndrome. Nevertheless, impressive successes have occurred, and several of these models are now being used widely for research. This, and many other recent studies have verified that Down syndrome has a genetically complex nature, but the mysteries of the condition are being unraveled systematically. Animal models have made extremely valuable contributions to these efforts, but, of course, mice are not people, and no matter how convincing, findings in mice need to be verified in people before firm conclusions about Down syndrome can be made. Therefore, researchers are desperately searching for volunteers to participate in studies focused on everything from the impact of Down Syndrome on the development of specific organ systems to promoting successful aging in affected individuals. In this article, the author discusses the great progresses made in the field of autism research through the use of animals and human subjects.