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Filamentous fungi produce a variety of secondary metabolites of diverse beneficial and detrimental activities to humankind. The genes required for a given secondary metabolite are typically arranged in a gene cluster. There is considerable evidence that secondary metabolite gene regulation is, in part, by transcriptional control through hierarchical levels of transcriptional regulatory elements involved in secondary metabolite cluster regulation. Identification of elements regulating secondary metabolism could potentially provide a means of increasing production of beneficial metabolites, decreasing production of detrimental metabolites, aid in the identification of ‘silent’ natural products and also contribute to a broader understanding of molecular mechanisms by which secondary metabolites are produced. This review summarizes regulation of secondary metabolism associated with transcriptional regulatory elements from a broad view as well as the tremendous advances in discovery of cryptic or novel secondary metabolites by genomic mining.