<p>Transposons populate the landscape of all eukaryotic genomes. Often considered purely genomic parasites, transposons can also benefit their hosts, playing roles in gene regulation and in genome organization and evolution. Peaceful coexistence with mobile elements depends upon adaptive control mechanisms, since unchecked transposon activity can impact long-term fitness and acutely reduce the fertility of progeny. Here, we review the conserved roles played by small RNAs in the adaptation of eukaryotes to coexist with their genomic colonists. An understanding of transposon-defense pathways has uncovered recurring themes in the mechanisms by which genomes distinguish “self” from “non-self” and selectively silence the latter.</p> <p>Transposons thrive as parasites of host genomes. When mobilized, they can disrupt protein-coding genes, alter transcriptional regulatory networks, and cause chromosomal breakage and large-scale genomic rearrangement (McClintock, 1951). Cells must therefore engage in an ongoing struggle to protect genomic integrity by guarding cellular DNA from the activity of mobile elements. Discriminating these parasites from a cell's own protein-coding genes is no small task. Individual transposons fall into many classes and bear little overall resemblance to each other. They employ myriad movement strategies, thus confounding any attempt to target a specific and distinguishable replication intermediate. Instead, our still emerging understanding points to a transposon defense that requires a working memory of each individual element. That memory appears to arise after initial colonization and a period of largely unregulated activity during which the mobility of the element, per se, is the Achilles' heel that insures its downfall. By jumping into specific loci, transposons become trapped in a silencing program that instructs a small RNA-based immune system to selectively silence homologous elements in germ cells, thus guarding the genetic integrity of the species.</p>