Cell‐wall‐less bacterial variants, or L‐forms, have been described in many bacterial species under laboratory conditions, in infected eukaryotic cell cultures and inside animals. Of special interest for human health is the formation of L‐forms as a consequence of specific antibiotic treatments, and the potential involvement of L‐forms in persistent and relapsing infections. An old enigma about L‐forms is how they can divide in the absence of cell wall synthesis, since septum formation is an essential requisite for cell division. However, the (...) classical definition of L‐forms as cell‐wall‐less bacterial variants may need a revision to accomodate recent observations by Richard d'Ari and coworkers:1 genetic and biochemical evidence indicates that E. coli L‐forms induced by β‐lactam antibiotics do contain small amounts of peptidoglycan, essential for their growth and probably required for septum formation. If these observations are extrapolated to all known L‐forms, the very concept of cell‐wall‐less bacteria may need revision, and be restricted to mycoplasmas and their relatives. BioEssays 29:1189–1191, 2007. © 2007 Wiley Periodicals, Inc. (shrink)