Bacterial persisters are genetically drug-susceptible, quiescent (non-growing or slow-growing) bacteria that survive in stressful environments such as antibiotic exposure, acidic conditions, or starvation. These cells can regrow after stress removal and remain susceptible to the same stress. Persisters are a major challenge in treating chronic and persistent infections, relapse infections, and biofilm infections. Understanding the molecular mechanisms of persister formation and survival is critical for developing more effective treatments. This review article summarizes the historical background, characteristics, and mechanisms of bacterial persisters, as well as the relationship between persisters and antibiotic-tolerant and -resistant bacteria. It also discusses the interplay between various bacterial biological processes and the formation of persister cells, and consolidates diverse anti-persister compounds and treatments. The article highlights the importance of persisters in clinical settings, particularly in infections such as tuberculosis, typhoid fever, and Lyme disease. It also discusses the challenges in detecting persisters, including the limitations of traditional methods like the time-kill assay and the need for more accurate detection techniques. The review emphasizes the role of toxin-antitoxin (TA) modules in persister formation, including the HipA, RelBE, MazEF, and DinJ-YafQ modules. These modules contribute to the formation of persisters by inhibiting replication and translation processes, leading to the survival of a subpopulation of bacteria under stress. The review also discusses the importance of understanding the molecular mechanisms of persister formation to develop new therapeutic strategies for treating persistent infections.Bacterial persisters are genetically drug-susceptible, quiescent (non-growing or slow-growing) bacteria that survive in stressful environments such as antibiotic exposure, acidic conditions, or starvation. These cells can regrow after stress removal and remain susceptible to the same stress. Persisters are a major challenge in treating chronic and persistent infections, relapse infections, and biofilm infections. Understanding the molecular mechanisms of persister formation and survival is critical for developing more effective treatments. This review article summarizes the historical background, characteristics, and mechanisms of bacterial persisters, as well as the relationship between persisters and antibiotic-tolerant and -resistant bacteria. It also discusses the interplay between various bacterial biological processes and the formation of persister cells, and consolidates diverse anti-persister compounds and treatments. The article highlights the importance of persisters in clinical settings, particularly in infections such as tuberculosis, typhoid fever, and Lyme disease. It also discusses the challenges in detecting persisters, including the limitations of traditional methods like the time-kill assay and the need for more accurate detection techniques. The review emphasizes the role of toxin-antitoxin (TA) modules in persister formation, including the HipA, RelBE, MazEF, and DinJ-YafQ modules. These modules contribute to the formation of persisters by inhibiting replication and translation processes, leading to the survival of a subpopulation of bacteria under stress. The review also discusses the importance of understanding the molecular mechanisms of persister formation to develop new therapeutic strategies for treating persistent infections.