It has become clear in the past few years that eukaryotic organisms possess different genetic systems to counter viruses, transposons and other repeated elements such as transgenes that could otherwise accumulate in the genome. In addition to serving as a model organism for genetic, biochemical and molecular studies, Neurospora crassa has proved to be a paradigm for the study of gene-silencing mechanisms. Indeed, its genome can be protected from expansion of selfish nucleic acids by a variety of mechanisms that inactivate duplicated sequences. Studies of these mechanisms have made a fundamental contribution to the understanding of the gene-silencing field.