Abstract:The growing bacteria drug resistance has seriously threatened the “antibiotic miracle”, while traditional approaches for new antibiotics discovery could not combat this problem and novel solutions are urgently needed. Recently, new methods and technologies such as novel screening model establishment, genome mining and combinatorial biosynthesis have revolutionized the screening of natural products. Applying these technologies offers a unique opportunity to re-establish actinobecteria as a major source for drug discovery. These new advances and technologies are described in this review.