Male infertility is one of the biggest concerns of today's health care community. In the US and other developed countries, approximately 70% of infertility among couples is attributed to male reproductive failure. Alterations in reproductive organ development and sperm production have been listed as the major causes of this phenomenon. Sex determination and differentiation, X chromosome inactivation, gene imprinting and normal germ cell development are important biological processes that, in turn, control mammalian reproduction. Specific patterns of gene expression and repression are important in such processes. The strong correlation between DNA methylation, a major epigenetic modification of the genome, and gene expression patterns is well documented. The effects of DNA methylation on the expression of genes affecting male reproductive organ development, spermatogenesis, and male sexual behavior have been reported, suggesting that alterations in DNA methylation could induce abnormal male sexual development and reproductive performance. Inheritance of epigenetic processes and changes in DNA methylation patterns induced by certain diets have been demonstrated in recent years. However, the effects of DNA methylation on male fertility have not been well studied. Since inherited altered DNA methylation patterns could be a cause of increased susceptibility to xenobiotics or abnormal phenotype in future generations, multigenerational studies oriented to determine the effects of xenobiotics affecting DNA methylation in male fertility are recommended.