AbstractOne‐carbon metabolism is involved in varieties of physiological processes in mammals, including nucleic acid synthesis, amino acid homeostasis, epigenetic regulation, redox balance and neurodevelopment. The current evidence linking levels of one‐carbon nutrients during pregnancy to the development of oocytes, embryos, and placentas, as well as maternal and offspring health, is reviewed. The sources of mammalian one‐carbon units, the pathways active in mammalian one‐carbon metabolism, the maternal and fetal needs for one‐carbon units and their functions during pregnancy are described. The demand for one‐carbon metabolism is highest during pregnancy compared to the entire lifetime of a mammal. The primary types of one‐carbon metabolism in mammals are the folate cycle, methionine cycle and transsulfuration pathway, which varies at different pregnancy stages (e.g., methylation programming of embryo, neural development of fetus, fetal growth and placenta development). Therefore, an overall consideration of one‐carbon metabolism requirements for different pregnancy stages, is called for, specifically, the balance of all nutrients involved, not just one single nutrient in one‐carbon metabolism. Moreover, the establishment of an ideal one‐carbon metabolism requirement model is suggested according to the requirements for different pregnancy stages to support optimal pregnancy outcomes and maternal and offspring health.