Streptomyces is a gram-positive filamentous actinomycete, which can produce many valuable secondary metabolites, such as antibiotics and immunomodulators. Streptomyces is known as the synthetic factory of natural medicine, and scientists have completed the sequencing of two Streptomyces strains. Compared with other prokaryotes, Streptomyces has complex morphological differentiation characteristics and can be used as a model organism for cell differentiation and development research. With the completion of genome sequencing of Streptomyces coelicolor and Streptomyces avermitilis, scientists found 24 gene clusters encoding secondary metabolites such as pigments in Streptomyces coelicolor and 30 such gene clusters in Streptomyces avermitilis. This amount is far more than the number of secondary metabolites found in these two Streptomyces species, but so many natural products can not be obtained by using the existing culture conditions and screening methods. The clarification of the regulation mechanism of secondary metabolism of Streptomyces will provide a theoretical basis for discovering more natural products. With the emergence and application of new technologies in genomics and protein genomics, we can analyze Streptomyces genome and protein group, establish physiological and mathematical models, and quantitatively analyze the expression of regulatory genes in time and space. The research on molecular regulation mechanism of secondary metabolism of Streptomyces will be greatly developed. The study of Streptomyces genome and secondary metabolic regulatory network will certainly promote the discovery of more new natural products.