The etiology of most human diseases involves complicated interactions of multiple environmental factors with individual genetic background which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Early embryogenesis includes a series of programming processes involving extremely accurate time-controlled gene activation/silencing expressions, and epigenetic control is believed to play a key role in regulating early embryonic development. Certain dietary components with properties in influencing epigenetic processes are believed to have preventive effects on many human diseases such as cancer. Evidence shows that in utero exposure to certain epigenetic diets may lead to reprogramming of primary epigenetic profiles such as DNA methylation and histone modifications on the key coding genes of the fetal genome, leading to different susceptibility to diseases later in life. In this review, we assess the current advances in dietary epigenetic intervention on transgenerational human disease control. Enhanced understanding of the important role of early life epigenetics control may lead to cost-effective translational chemopreventive potential by appropriate administration of prenatal and/or postnatal dietary supplements leading to early disease prevention. © 2013 American Association of Pharmaceutical Scientists.