With the development of sequencing technology and further scientific research, an increasing number of biosynthetic gene clusters associated with secondary metabolites have been identified and characterized. The encoded genes of a family of regulators designated as PAS-LuxR are gradually being discovered in some biosynthetic gene clusters of polyene macrolide, aminoglycoside, and amino acid analogues. PAS-LuxR family regulators affect secondary metabolites by interacting with other family regulators to regulate the transcription of the target genes in the gene cluster. This paper provides a review of the structure, function, regulatory mechanism, and application of these regulators to provide more information on the regulation of secondary metabolite biosynthesis in and promote the application of PAS-LuxR family regulators in industrial breeding and other directions.