This chapter traces the development of the concept of heredity and, in particular, shows how that development has shed light on the host of hereditary and genetic diseases people have come to recognize in humans. It discusses some basic-concepts and terms, and reviews the study of genetic disease from the Greeks to Garrod and the impact of Mendelism. The chapter outlines the heuristic model of genetic transmission that has come to be the standard of modern medical genetics. The most recent development in the study of human genetic diseases is traced through three specific examples. First, sickle cell anemia, represents a triumph of the molecular-model of human disease. The discovery of the second, Down syndrome, reveals the role in medical genetics of the cytogeneticist, who studies chromosomes. The third, kuru, exemplifies a case in which the expectations of modern medical genetics led initially to an erroneous conclusion, although that failure led eventually to spectacular new knowledge.