The early stages of embryonic development in all metazoans are characterized by profound remodeling of chromatin organization and transcriptomics. This remodeling involves modifying two differentiated cells (oocyte and sperm) into a totipotent embryonic configuration capable of forming all the specialized cells that make up the adult animal. The early cleavage stages of preimplantation animal embryos occur in the absence of active transcription and relies on maternal factors stored in the cytoplasm of the oocyte during oogenesis. Chromatin and transcriptomic remodeling during preimplantation development are key for the initiation of embryonic transcriptional activity at species-specific stage, yet the exact mechanisms that trigger embryonic genome activation (EGA) are still unknown. Evidence of key transcriptional regulators and permissive chromatin configuration accompanied by specific epigenetic marks has been revealed as some of the mechanisms needed for EGA in the past few years. In this review, we will revisit the latest advances in the understanding of the mechanisms involved in the activation of the embryonic genome across several species, focusing on data generated by next generation sequencing technologies.