Microbial natural products are an important source of new drug creation. As more and more microbial whole genomes are sequenced, bioinformatics analysis shows that the natural prod-uct resources contained therein are greatly underestimated. Genome mining is a new strategy for natural product discovery guided by gene cluster sequences. At the same time, it can di-rectly associate the structure of natural products with synthesis pathways, which is conven-ient for biosynthesis and combinatorial biosynthesis research. This paper reviews the repre-sentative examples of successful discovery of novel natural products using genome mining strategy in recent years, which fully shows the great advantage of this strategy in exploring the potential of microbial natural metabolites. It is believed that with the continuous devel-opment and improvement of genome mining methods and technologies, it will be possible to realize the in-depth development of microbial natural product resources.This paper describes the application of combinatorial biosynthesis in new drugs, points out the existing problems and puts forward some feasible suggestions.