ABSTRACTLactic acid bacteria (LAB) encompasses industrially relevant bacteria involved in food fermentations as well as health-promoting members of our autochthonous microbiota. In the last years, we have witnessed major progresses in the knowledge of the biology of their cell wall, the outermost macrostructure of a Gram-positive cell, which is crucial for survival. Sophisticated biochemical analyses combined with mutation strategies have been applied to unravel biosynthetic routes that sustain the inter- and intra-species cell wall diversity within LAB. Interplay with global cell metabolism has been deciphered that improved our fundamental understanding of the plasticity of the cell wall during growth. The cell wall is also decisive for the antimicrobial activity of many bacteriocins, for bacteriophage infection and for the interactions with the external environment. Therefore, genetic circuits involved in monitoring cell wall damage have been described in LAB, together with a plethora of defence mechanisms that help them to cope with external threats and adapt to harsh conditions. Since the cell wall plays a pivotal role in several technological and health-promoting traits of LAB, we anticipate that this knowledge will pave the way for the future development and extended applications of LAB.