A class of 24-32 nt PIWI-binding small noncoding RNAs (sncRNAs) termed as PIWI-interacting RNAs (piRNAs) have been identified in animal germline. Recent studies suggest that piRNA/PIWI pathway plays a critical role in both silencing of transposons and posttranscriptional regulation of mRNAs in animal germline. A study from Dr. Mofang Liu's lab in Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, reveals the physiological and pathological importance of PIWI metabolism (mouse PIWI as known as MIWI; human PIWI as HIWI) in mammalian spermatogenesis. Here, we summarize our current understanding of the piRNA/PIWI pathway in mammals (focusing on mouse and human), which is emerging as a fundamental component of spermatogenesis that ensures male fertility and genome integrity.