With the inappropriate use of antibiotics, the situation of bacterial resistance is more and more severe. The emergence of multidrug-resistant (MDR) bacteria has made it difficult to cure the infections in clinical. For treatment the infections caused by MDR and reducucton of the generation of resistant bacteria, researchers are actively studying on the non-antibiotic substances for antibacterial activity. In this paper, the advances in those with conifrmed effects such as phage therapy, metal/chelation therapy, immunization therapy, photodynamic therapy, and nitric oxide (NO)-based therapies, small molecule inhibitors, antimicrobial peptides and Chinese herb were reviewed.