This review article by Niu, Gu, and Zhang provides a comprehensive overview of bacterial persisters, their molecular mechanisms, and therapeutic development. Persisters are genetically drug-susceptible bacteria that survive under stressful conditions such as antibiotic exposure, acidic environments, or starvation. They can regrow after stress removal and remain susceptible to the same stress, posing significant challenges in treating chronic and persistent infections, drug resistance, and biofilm infections. The article highlights the importance of understanding the characteristics and mechanisms of persister formation, particularly the key molecules involved in their survival and formation. The authors discuss the historical background of bacterial persisters, detailing their complex characteristics and their relationship with antibiotic-tolerant and resistant bacteria. They systematically elucidate the interplay between various bacterial biological processes and the formation of persister cells, and consolidate diverse anti-persister compounds and treatments. The review aims to provide a theoretical background for in-depth research on persister mechanisms and suggest new strategies for more effective treatment of persistent infections. Key points include: - The discovery and significance of bacterial persisters in chronic infections. - The distinction between persisters, resistant bacteria, and tolerant bacteria. - Methods for detecting persister cells, such as time-kill assays, MDK99/MDK99.99, ScanLag, CoTapp, Tolerance Disk Test (TDtest), and Replica Plating Tolerance Isolation System (REPTIS). - The role of persisters in the recurrence of infections, bacterial resistance, and biofilm infections. - Molecular mechanisms of persister formation, including toxin-antitoxin modules (TA modules) and energy metabolism. - The challenges and potential therapeutic targets in developing anti-persister treatments. The article emphasizes the need for further research to improve detection methods and develop more effective treatments for persistent infections.This review article by Niu, Gu, and Zhang provides a comprehensive overview of bacterial persisters, their molecular mechanisms, and therapeutic development. Persisters are genetically drug-susceptible bacteria that survive under stressful conditions such as antibiotic exposure, acidic environments, or starvation. They can regrow after stress removal and remain susceptible to the same stress, posing significant challenges in treating chronic and persistent infections, drug resistance, and biofilm infections. The article highlights the importance of understanding the characteristics and mechanisms of persister formation, particularly the key molecules involved in their survival and formation. The authors discuss the historical background of bacterial persisters, detailing their complex characteristics and their relationship with antibiotic-tolerant and resistant bacteria. They systematically elucidate the interplay between various bacterial biological processes and the formation of persister cells, and consolidate diverse anti-persister compounds and treatments. The review aims to provide a theoretical background for in-depth research on persister mechanisms and suggest new strategies for more effective treatment of persistent infections. Key points include: - The discovery and significance of bacterial persisters in chronic infections. - The distinction between persisters, resistant bacteria, and tolerant bacteria. - Methods for detecting persister cells, such as time-kill assays, MDK99/MDK99.99, ScanLag, CoTapp, Tolerance Disk Test (TDtest), and Replica Plating Tolerance Isolation System (REPTIS). - The role of persisters in the recurrence of infections, bacterial resistance, and biofilm infections. - Molecular mechanisms of persister formation, including toxin-antitoxin modules (TA modules) and energy metabolism. - The challenges and potential therapeutic targets in developing anti-persister treatments. The article emphasizes the need for further research to improve detection methods and develop more effective treatments for persistent infections.