Transposable elements or transposons are DNA pieces that can move around within the genome and are, therefore, potential threat to genome stability and faithful transmission of the genetic information in the germline. Accordingly, self-defense mechanisms have evolved in the metazoan germline to silence transposons, and the primary mechanism requires the germline-specific non-coding small RNAs, named Piwi-interacting RNA (piRNAs), which are in complex with Argonaute family of PIWI proteins (the piRNA-RISC complexes), to silence transposons. piRNA-mediated transposon silencing occurs at both transcriptional and post-transcriptional levels. With the advantages of genetic manipulation and advances of sequencing technology, much progress has been made on the molecular mechanisms of piRNA-mediated transposon silencing in Drosophila melanogaster, which will be the focus of this review. Because piRNA-mediated transposon silencing is evolutionarily conserved in metazoan, model organisms, such as Drosophila, will continue to be served as pioneer systems towards the complete understanding of transposon silencing in the metazoan germline.