The maternal to zygotic transition is the first major transition that occurs following fertilization, and entails a dramatic reprogramming of gene expression that is essential for continued development. Although the major reprogramming of gene expression occurs during the 2-cell stage, transcription is evident in the 1-cell embryo, with the male pronucleus supporting a significantly higher level of transcription than the female pronucleus. This difference is likely due to differences in chromatin structure as a consequence of the protamine–histone exchange. Although the 1-cell embryo is transcriptionally competent, transcription and translation appear uncoupled. This transcription, however, may mark promoters for efficient utilization in the 2-cell embryo. Genome activation in the 2-cell embryo is accompanied by a requirement for an enhancer for efficient transcription and the more efficient utilization of TATA-less promoters. These changes in promoter utilization could contribute substantially to the reprogramming of gene expression. Superimposed on genome activation is the development of a chromatin-mediated transcriptionally repressive state that is relieved by either inducing histone hyperacetylation or inhibiting the second round of DNA replication. Since genome activation appears to be a relatively opportunistic process, the development of the transcriptionally repressive state may be a major determinant in establishing the appropriate gene expression profile that is essential for continued development.