Abstract <p>Bacteria enter the L-form state after shedding their cell walls in response to adverse conditions for survival; these bacteria can revert to their walled morphology after the unfavorable factors are removed. Bacterial L-forms can be either unstable (typically observed in clinically isolated and induced L-forms) or stable (associated with two specific mutation types). In recent years, bacterial L-forms have been implicated in antibiotic resistance, disease recurrence, and origin of life. However, because identifying bacterial L-forms is difficult, they are often overlooked in clinical settings. In this review, we elucidate the relationships of bacterial L-forms with their cell walls, mutation, proliferation, antibiotic resistance, and disease recurrence, as well as with the host immune system. We also highlight the challenges and future prospects for bacterial L-form research.</p> Graphical Abstract <p></p>