The correlation between epigenetics and human reproduction represents a very interesting field of study, mainly due to the possible transgenerational effects related to epigenetic modifications of male and female gametes. In the present review, we focused our attention to the role played by epigenetics on male reproduction, evidencing at least four different levels at which sperm epigenetic modifications could affect reproduction: (1) spermatogenesis failure; (2) embryo development; (3) outcome of assisted reproduction technique (ART) protocols, mainly as concerning genomic imprinting; and (4) long-term effects during the offspring lifetime. The environmental agents responsible for epigenetic modifications are also examined, suggesting that the control of paternal lifestyle prior to conception could represent in the next future a novel hot topic in the management of human reproduction.