Epigenetics provides a means of understanding how environmental factors might alter heritable changes in gene expression without changing DNA sequence, and hence the origin, of some diseases that are not explained by conventional genetic mechanisms. Various animal models have been described, most notably the agouti viable yellow (A(vy)) and axin 1 fused (Axin1(Fu)) mice, which lend themselves particularly well to studying this link between epigenetics and development abnormalities, because particular changes in DNA methylation patterns can be linked to a broad spectrum of heritable pathologies in the mice. In addition, there are specific examples, both in mice and other animal species, where nonmutagenic, environmental insults to either parent, such as those caused by consumption of endocrine-disrupting chemicals, can cause unexpected transgenerational phenotypic changes in offspring. Animals derived by somatic cell nuclear transfer also frequently exhibit pathologies that can be linked to inappropriate nuclear reprogramming during early embryo development and provide another means to study a link between epigenetics and disease. This review will consider how all of these animal models might help elucidate the epigenetic basis for a wide range of phenotypes.