Filamentous fungi are today a major source of industrial biotechnology for the production of primary and secondary metabolites, as well as enzymes and recombinant proteins. All of them have undergone extensive improvement strain programs, initially by classical mutagenesis and later on by genetic manipulation. Thereby, strategies to overcome rate-limiting or yield-reducing reactions included manipulating the expression of individual genes, their regulatory genes, and also their function. Yet, research of the last decade clearly showed that cells can also undergo heritable changes in gene expression that do not involve changes in the underlying DNA sequences (=epigenetics). This involves three levels of regulation: (i) DNA methylation, (ii) chromatin remodeling by histone modification, and (iii) RNA interference. The demonstration of the occurrence of these processes in fungal model organisms such as Aspergillus nidulans and Neurospora crassa has stimulated its recent investigation as a tool for strain improvement in industrially used fungi. This review describes the progress that has thereby been obtained.