Sexual reproduction in mammals requires production and subsequent fusion of functional gametes originating from individuals of opposite sex, in order to perpetuate the species. In male mammals, production of spermatozoa occurs in the testis throughout the biological process named spermatogenesis. MicroRNAs and endogenous small-interfering RNAs inhibit the protein synthesis by silencing both the translation initiation and elongation or by activating the mRNA degradation. Their biogenesis depends on DICER1. We developed a transgenic mouse model in which the Dicer1 gene was inactivated in a specific and fully penetrant manner in the male germ cell lineage. Our results indicate that Dicer1 is required for completion of normal spermatogenesis, since its deletion leads to cumulative defects in meiosis and spermiogenesis resulting in the absence of functional spermatozoa and thus to complete infertility. In this perspective, we opened a new path in germ cells biology that might unravel certain issues of male infertility.