Non-tuberculous mycobacteria (NTM) cause chronic pulmonary infections in individuals with cystic fibrosis, and antibiotic-resistant NTM (for example, Mycobacterium abscessus) is widespread. The use of phages to treat drug-resistant bacterial infections is a potential alternative strategy. Dedrick et al. report the use of a three-phage cocktail in the treatment of disseminated drug-resistant M. abscessus. After an uncomplicated bilateral lung transplant in a 15-year-old patient with cystic fibrosis, the patient was diagnosed with a disseminated drug-resistant M. abscessus subsp. massiliense infection, necessitating an alternative treatment strategy. The authors used screening, genome engineering and forward genetics to develop a cocktail of three lytic phage derivatives that efficiently kill the infectious M. abscessus strain. Intravenous administration of the cocktail was well-tolerated and resulted in clinical improvements — sternal wound closure, improved liver function and substantial resolution of infected skin lesions.