Mammals, like all multicellular organisms, develop from a single cell—the totipotent zygote. During preimplantation development and subsequent development in utero, over 200 distinct cell types are established and integrated into the organ systems and tissues of the developing organism. Much of the field of mammalian developmental biology is devoted to investigation of mechanisms that govern the formation of complete organs and tissues. In contrast to later development, which consumes the vast majority of time associated with development in utero, preimplantation development and germ layer specification occur rapidly. Yet knowledge is limited regarding the regulatory mechanisms that specify the transient, but pluripotent, cellular lineages that form during the initial stages of mammalian development. Gametogenesis and preimplantation development are marked by dramatic and pervasive epigenetic changes rooted in chromatin dynamics. The fundamental mechanisms that specify subsequent cellular lineages of the conceptus are only now becoming understood, and tend to rely relatively heavily upon broad epigenetic mechanisms in addition to master transcription factors. This review considers epigenetic regulation in the very earliest stages of preimplantation development. In addition, recent advances which indicate that some epigenetic coding is imposed during gametogenesis and maintained during preimplantation development are considered. J. Cell. Physiol. 225: 333–336, 2010. © 2010 Wiley-Liss, Inc.