Appropriate regulation of epigenome within cells is crucial for the determination of cell fate and contributes to the lifelong maintenance of tissue homeostasis. Epigenomic re-establishment during embryonic prospermatogonia development and fine-tune of the epigenetic landscape in postnatal spermatogonial stem cells (SSCs) are two key processes required for functional male germ cell formation. Repression of re-activated transposons and male germline-specific epigenome establishment occur in prospermatogonia, whereas modulations of the epigenetic landscape is important for SSC self-renewal and differentiation to maintain the stem cell pool and support long-term sperm production. Here, we describe the impact of epigenome-related regulators and small non-coding RNAs as well as the influence of epigenome modifications that result from extrinsic signaling for controlling the decision between self-renewal, differentiation and survival in mouse prospermatogonia and SSCs. This article provides a review of epigenome-related molecules involved in cell fate determination in male germ cells and discusses the intriguing questions that arise from these studies.