Mycobacterium abscessus is an emerging cause of respiratory disease and soft tissue infections. Whole genome sequencing and other molecular approaches are enhancing our understanding of outbreaks, antibiotic resistance mechanisms, and virulence properties, and of the phylogeny of the M. abscessus complex. Infection models are providing further insights into factors such as colony phenotype that impact host-pathogen interactions. This paper reviews recent developments in our understanding of genetic variation in M. abscessus and the potential relevance for disease and treatment.