The elucidation, unravelling and understanding of the molecular basis of transcriptional control during preimplantion development is of utmost importance if we are to intervene and eliminate or reduce abnormalities associated with growth, disease and infertility by applying assisted reproduction. Importantly, these studies should enhance our knowledge of basic reproductive biology and its application to regenerative medicine and livestock production. A major obstacle impeding progress in these areas is the ability to successfully generate molecular portraits of preimplantation embryos from their minute amounts of RNA. The present review describes the various approaches whereby classical embryology fuses with molecular biology, high-throughput genomics and systems biology to address and solve questions related to early development in mammals.