The increasing interest in metagenomics is enhancing our knowledge regarding the composition and role of the microbiota in human physiology and pathology. Indeed, microbes have been reported to play a role in several diseases, including infertility. In particular, the male seminal microbiota has been suggested as an important factor able to influence couple’s health and pregnancy outcomes, as well as offspring health. Nevertheless, few studies have been carried out to date to deeper investigate semen microbiome origins and functions, and its correlations with the partner’s reproductive tract microbiome. Here, we report the state of the art regarding the male reproductive system microbiome and its alterations in infertility.