Histone chaperones are fundamental molecules that aid in the synthesis, translocation, and exchange of histones across the barrier of cytoplasm to nucleus. Regulation in repair, replication, and nucleosome assembly constitute the widely associated functions of histone chaperones. Recently, they have been associated with transcriptional regulation. Different stages of mammalian development have been correlated to the expression of histone chaperones. From oocyte and sperm till the formation and development of zygote, different histone chaperones demonstrated distinct regulatory roles. Efficient models of studying mammalian development include differentiation of embryonic stem cells (ESCs) to different lineages. Both in vitro and in vivo differentiation of mammalian cells exhibit regulation by different subtypes of histone chaperones. Due to the ethical issues concerning the use of embryos for the derivation of ESCs, induced pluripotent stem cells (iPSCs) were derived from pre-existing differentiated cells by a phenomenon called cellular reprogramming. Cellular reprogramming is characterized by erasure of pre-existing epigenetic signature to a new modulated epigenome. Histone chaperones serve as either facilitator or barrier to reprogramming. Here, we will discuss how histone chaperones could regulate the gene expression pattern by regulating epigenetic modification during the complex process of mammalian development and reprogramming