Public Library of Science ; Background Preimplantation development is a crucial step in early human development. However, the molecular basis of human preimplantation development is not well known. Methodology By applying microarray on 397 human oocytes and embryos at six developmental stages, we studied the transcription dynamics during human preimplantation development. Principal Findings We found that the preimplantation development consisted of two main transitions: from metaphase-II oocyte to 4-cell embryo where mainly the maternal genes were expressed, and from 8-cell embryo to blastocyst with down-regulation of the maternal genes and up-regulation of embryonic genes. Human preimplantation development proved relatively autonomous. Genes predominantly expressed in oocytes and embryos are well conserved during evolution. Significance Our database and findings provide fundamental resources for understanding the genetic network controlling early human development.