The long-term effects of in vitro embryo culture on animal health are presently unknown, however, current knowledge directs investigations toward understanding the mechanisms involved in regulating embryo development. In vitro culture is known to have short-term effects, particularly on gene expression and metabolism at the blastocyst stage, while large offspring syndrome is commonly observed following transfer of in vitro produced bovine embryos. Indeed, it is likely that the environment surrounding the early embryo, prior to implantation, may program later development. Regulation of gene expression and metabolism, through gene activation, is mediated by transcription factors, which are themselves controlled by internal and external factors. Alterations in the surrounding environment during preimplantation embryo development, such as that which occurs with inadequate developmental 'support' during in vitro culture, may modify the activation, or inactivation, of several transcription factors, and may therefore have long-term consequences for the developing offspring. In vitro culture deviates from in vivo conditions in many respects, but one of the critical factors that is generally not considered is the oxygen tension under which embryos are cultured. Numerous studies have demonstrated that atmospheric oxygen conditions during culture have detrimental effects on embryo development. While it is generally believed that this arises from the production of reactive oxygen species, this presents an over-simplistic view of the role of oxygen during development. The hypoxia-inducible factor transcription factor family is involved in the responses of cells to alterations in external oxygen concentrations, regulating the expression of numerous genes. Alterations in expression of some of these genes have been highlighted by recent studies in the bovine embryo, implicating oxygen as a regulator of several cellular and metabolic pathways. While it is clear that oxygen plays a role during embryo development, further work to investigate interactions between oxygen and other signaling pathways such as pH and Ca(2+), mitochondria and metabolism is required, as well as exposure of embryos at different time points, to determine the mechanisms that control preimplantation development, the interactions of a range of stimuli and to establish culture procedures that support optimal development and minimize risks to health. This review focuses largely on work undertaken in ruminant models, with brief references to other species.