Molecular genetic approaches have advantages in investigating various physiological aspects of mushrooms. We have been engaged in developing genetic transformation system mainly in wood rot mushrooms. In this presentation, our recent trials to accelerate mushroom science beyond the post-genomic era will be presented. They include development of research tools both in forward and reverse genetics; a transfection system and its utilization in gene expression signal analysis in the selective white rot fungus Ceriporiopsis subvermispora, multiple gene targeting system in Pleurotus ostreatus and Coprinopsis cinerea, which was used to do knock-out or knock-in of reporter constructs on the chromosome of these fungi, and a “powered” forward genetics combined with genome information was used to identify new gene responsible for lignin-degradation in P. ostreatus. They may contribute to elucidate uncovered molecular mechanisms in unique processes in the mushrooms and to make them as a new industrial tool in the next era. Furthermore, our recent results in on-going genome editing experiments will be also reported.