Fungal secondary metabolites are of intense interest to humankind due to their pharmaceutical (antibiotics) and/or toxic (mycotoxins) properties. In the past decade, tremendous progress has been made in understanding the genes that are associated with production of various fungal secondary metabolites. Moreover, the regulatory mechanisms controlling biosynthesis of diverse groups of secondary metabolites have been unveiled. In this review, we present the current understanding of the genetic regulation of secondary metabolism from clustering of biosynthetic genes to global regulators balancing growth, sporulation, and secondary metabolite production in selected fungi with emphasis on regulation of metabolites of agricultural concern. Particularly, the roles of G protein signaling components and developmental regulators in the mycotoxin sterigmatocystin biosynthesis in the model fungus Aspergillus nidulans are discussed in depth.