In this chapter, we will present nutritional epigenetics as a subdiscipline of nutrigenomics and describe how dietary compounds affect our epigenome. Different epigenetic mechanisms, such as post-translational histone modifications and DNA methylation, process information provided by dietary molecules. Accordingly, many chromatin modifiers use intermediary metabolites, such as acetyl-CoA, α-ketoglutarate, NAD+ or ATP, as co-substrates and/or co-factors. Thus, these enzymes act as sensors for the nutritional status of our tissues and cell types leaving respective marks on their epigenome. Prenatal supplementation in mice as well as natural human experiments provide insight into the concepts of epigenetic programming during embryogenesis and epigenetic drift during adult life. This may explain some of the susceptibility for complex metabolic diseases, such as T2D.