Mental retardation is a condition with multiple, disparate causes, both environmental and genetic. In this article we have tried to characterize, in a general fashion, the nature of the genetic factors through a discussion of polygenic inheritance, single gene errors, and chromosomal anomalies. Despite the existence of a large and complex body of knowledge, which has only been touched upon here, it is sobering to realize that we cannot diagnose almost half of the mentally retarded. Even in those in whom a genetic etiology is obvious, we know little about the intervening processes that operate between the gene and the mental deficiency it produces. Under the conditions, therapy holds little promise, while prevention assumes a high priority. Prevention of mental retardation due to genetic factors requires the physician to have a basis knowledge of genetic principles and syndromes, of prenatal diagnostic technology, and a determination to inform, even when the patient does not ask.