Mammalian development commences with the totipotent zygote, which is capable of developing into all the specialized cells that make up a whole organism, as well as into the extraembryonic support structures necessary for fetal development. Early embryonic blastomeres, up to at least the 4-cell stage embryo, also retain totipotency. Pluripotent cells in the inner cell mass (ICM) of blastocysts are the descendants of totipotent cells and can differentiate into any cell type except some extraembryonic tissues of the trophectodermal origin. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient’s own somatic cells can be used to make stem cells thereby eliminating immune based rejection of transplanted cells. The ability to contribute to chimeras upon reintroduction into host embryos is the key feature of murine totipotent and pluripotent cells. We recently demonstrated that rhesus monkey ESCs failed to incorporate into host embryos and develop into chimeras. However, ICMs transplanted into blastocysts formed separate viable fetuses while sharing the placental compartment of the host embryo. Classical monkey chimeras were produced by aggregation of totipotent cells of the 4-cell embryos. Currently, there is little known about human and nonhuman primate embryo development and lineage specification and how closely the mouse development reflects primates. Our study presents a first glimpse at the similarities and differences between mouse and primate preimplantation embryo development and offers an important experimental model to investigate lineage commitment and interactions.