Epigenetic reprogramming of chromatin, mediated through modifications to canonical histones and the incorporation of histone variants, plays a central role in the establishment of cell identity and regulation of gene expression programs. Such epigenetic programming becomes particularly important during the development of highly specialized cell types such as germ cells—sperm and oocytes, and stem cells within the blastula of early embryos. Determining patterns of epigenetic modifications within these cell types can be particularly challenging due to technical limitations associated with limited starting materials. Here we present a brief overview of studies focused on epigenetic reprogramming during the transition from sperm to blastula stage embryos and compare between several diverse model systems including Drosophila, zebrafish and mammals. Furthermore, we discuss and compare prevailing genomic profiling approaches, such as ChIP-Seq, CUT&Tag, and CUT&RUN, for performing genome-wide epigenomic analysis.