The development of all low-order animals and noneutherian mammals follows an organized, polarized directional course from fertilization through fetal development. New evidence points to a fundamental polarization during all steps of mammalian development, from the early oocyte through fertilization and gastrulation. The generator of this polarization is primarily at the genetic level, with the results of gene expression and checkpoints being manifested in phenotype. Although cell-cell interactions reinforce the polarization of the embryo, they are not the underlying means of establishing axes in eutherian embryos. The ability of mammalian cells to remain totipotent is only partial, with little evidence that isolated blastomeres can result in full fetal development. The isolated blastomere can, however, contribute to development if reintroduced into a polarized environment. Polarization begins in the unovulated oocyte and is reinforced at fertilization. The axes and polarization established at fertilization endure through to the blastocyst stage and define the axes during gastrulation and fetal development.