In this chapter we describe a method to generate mutants of filamentous fungi using their genomic plasticity and rapid adaptability to their environment. This method is based on spontaneous mutations occurring in relation to improved growth of fungi on media by repeated inoculation resulting in adaptation of the strain to the condition. The critical aspect of this method is the design of the selective media, which will depend strongly on the phenomenon that will be studied. This method is advantageous over UV or chemical random mutagenesis as it results in a lower frequency of undesired mutations and can result in strains that combined with (post)genomic approaches can enhance our understanding of the mechanisms driving various biological processes. In addition, it can be used to obtain better strains for various industrial applications. The method described here is specific for sporulating fungi and has so far not yet been tested for nonsporulating fungi.