Abstract: Fungi-derived secondary metabolites have always been an important source of natural medicines. However, the sucess rate for discovering new compounds from fungi is decreasing. In recent years, the rapid advancement of next-generation sequencing technologies enables the genomic data of diverse fungal species to be accessible. Bioinformatics analysis demonstrates that the number of gene clusters encoding natural products in fungal genome is much larger than the number of identified natural products, revealing that there are plenty of silent gene clusters in fungi. Therefore, for the deep utilization of fungal resources in the post-genomic era, the key issue is how to efficiently activate silent gene clusters. In this paper, we summarize the research progress in strategies for activating fungal silent gene clusters, aiming to provide a reference for the efficient use of fungal resources.