Transposable elements and their fossil sequences occupy about half of the genome in mammals. While most of these selfish mobile elements have been inactivated by truncations and mutations during evolution, some copies remain competent to transpose and/or amplify, posing an ongoing genetic threat. To control such mutagenic sequences, host genomes have developed multiple layers of defence mechanisms, including epigenetic regulation and RNA silencing. Germ cells, in particular, employ the piwi-small RNA pathway, which plays a central and adaptive role in safeguarding the germline genome from retrotransposons. Recent studies have revealed that a class of developmentally regulated genes, which have long been implicated in germ cell specification and differentiation, such as vasa and tudor family genes, play key roles in the piwi pathway to suppress retrotransposons, indicating that the piwi-mediated genome protection is at the core of germline development. Furthermore, while the piwi system primarily operates post-transcriptionally at the RNA level, it also affects the epigenetics of cognate genome loci, offering an intriguing link between small RNAs and transcriptional control in mammals. In this review, we summarize our current understanding of the piwi pathway in mice, which is emerging as a fundamental component of spermatogenesis that ensures male fertility and genome integrity.