Daptomycin, produced by Streptomyces roseosporus, is a novel cyclic lipopeptide antibiotic against Gram-positive pathogenic bacteria. It is regarded as a potent antibiotic following vancomycin, the last defense line of antibiotics. This review summarizes the research advances of daptomycin in recent years, mainly including structure, action mechanism, biosynthesis and genes involved in biosynthesis of daptomycin. The strategies of combinatorial biosynthesis are also reviewed to study the relationship between structure and the anti-microbial activity to find potent daptomycin derivatives with a wider spectrum and higher anti-microbial activities. Finally, some strategies to improve daptomycin yields are also introduced, which will be the basis to reduce the daptomycin cost in industrial production.