Mycobacterium abscessusis a nontuberculosis mycobacterium (NTM) that has shown an exponential rise in its ability to cause disease. Due to its ubiquitous presence in the environment,M.abscessusis widely implicated in secondary exacerbations of many nosocomial infections and genetic respiratory disorders, such as cystic fibrosis (CF). Contrary to other rapidly growing NTMs, the cell envelope ofM.abscessusharbors several prominent features and undergoes modifications that are responsible for its pathogenesis. Compositional changes of the mycobacterial outer membrane (MOM) significantly decrease the presence of glycopeptidolipids (GPLs) and enable the transition from a colonizing, smooth morphotype into a virulent, rough morphotype. The GPLs are transported to the MOM by the Mycobacterial membrane proteins Large (MmpL), which further act as drug efflux pumps and confer antibiotic resistance. Lastly,M.abscessuspossesses 2 type VII secretion systems (T7SS): ESX-3 and ESX-4, both of which have recently been implicated in host–pathogen interactions and virulence. This review summarizes the current knowledge ofM.abscessuspathogenesis and highlights the clinically relevant association between the structure and functions of its cell envelope.