Mycobacterium tuberculosis, which is the aetiological agent of tuberculosis, owes much of its success as a pathogen to its unique cell wall and unusual mechanism of growth, which facilitate its adaptation to the human host and could have a role in clinical latency. Asymmetric growth and division increase population heterogeneity, which may promote antibiotic tolerance and the fitness of single cells. In this Review, we describe the unusual mechanisms of mycobacterial growth, cell wall biogenesis and division, and discuss how these processes might affect the survival of M. tuberculosis in vivo and contribute to the persistence of infection.