Familial aggregation of complex diseases may have many causes in addition to and apart from genetic predisposition due to common ancestry. For example, exposure to an environment that induces susceptibility to a disease may produce similar familial aggregations when the environment is shared by family members. In general, according to the principles of (Johannsen 1903), the emergence of a disease phenotype is the result of the combined effects of the genotype of the individual and the environment that it experiences during development. The heritability of a disease is a measure of familial aggregation in terms of the covariances among family members relative to the variance in disease state in the general population. Thus heritability expresses the within-family resemblance, observed by Darwin and inferred by him to reflect inheritance, which formed the core of his (Darwin 1859) theory of evolution. Darwin’s inspiration originated from the practical use of family resemblance in animal breeding. Animal breeders have long known that a major obstacle to progress in genetic improvement is the interaction between familial aggregation of environments and the effects of similar genetics within families. The potential importance of this interaction, recognized in classical studies of the genetic epidemiology of complex diseases and other quantitative characters, has reemerged in studies of the effects of epigenetic modifications, their variation, and their transmission between generations.