Recent research has associated metabolic diseases such as diabetes and obesity with a combination of genetic susceptibility and environmental factors or life style. In this combination, mechanisms involving molecules like non-coding RNAs and epigenetic marks like DNA methylation and histone posttranslational modifications have been proposed to act as a molecular bridge between dietary conditions and the genome. Through these mechanisms, dietary changes can influence the genome and in some cases, leave traces that persist across life and can be passed to the progeny. This chapter describes reported cases of inter- or transgenerational transmission of metabolic symptoms resulting from compromised dietary conditions in early life or adulthood in experimental animals and humans. It proposes possible molecular ways by which metabolic signals can influence the epigenome in different cells.