Streptomyces and other actinobacteria are important sources for bioactive products. In the light of whole genome sequencing technology, people have gained further information about Streptomyces. There exists a plethora of secondary metabolic pathways in Streptomyces, which exceeds the number of natural products that have been isolated under normal laboratory conditions. The expression of secondary metabolic pathways is regulated by a precise and sophisticated regulatory network. TetR family in Streptomyces is of great value in the regulatory network due to its huge number and multifunction. TetR family members could sense the environment changes through binding to specific GBL (gamma butyrolactone) molecules or other ligands with the help of the ligand binding domain, and subsequently repress or activate secondary pathways through regulating the expression of downstream target genes. This review will focus on the classification of TetR family proteins in Streptomyces based on their function and ligands they bind, and list the regulatory mechanism of known TFRs (TetR family regulators) on secondary metabolism in Streptomyces.