Abstract: Last two decades have witnessed the resurging of tuberculosis (TB) and multi-drug resistant TB, even the extensive drug resistant TB. It is urgent to develop novel drug to combat the increasingly worsen TB. Capreomycin is an ideal second-line TB drug. It is also recognized as an attractive template to develop more peptide antibiotics. In this review, the biosynthesis gene cluster of capreomycin, the action mechanism unveiled by transcriptome and novel resistance rational are summarized from the recent functional genomic investigation.