<p>Epigenetics studies heritable changes in gene expression without altering the DNA sequence and is involved in diverse biological processes. In male reproduction, Leydig cells, the main site of testosterone synthesis, play an important role in maintaining the reproductive process. However, the role of epigenetics in the mechanism of testosterone synthesis in Leydig cells is still not well understood. This review systematically describes how classic epigenetic modifications such as DNA methylation, RNA methylation, histone modification, and non-coding RNA regulate the testosterone synthesis process of Leydig cells in different species. Accumulating evidences revealed that epigenetics can regulate the process of testosterone synthesis in Leydig cells. In future, we aim to provide new ideas for male reproduction by investigating the relationship between testosterone synthesis mechanisms and epigenetics.</p>