Non-tuberculous mycobacterial (NTM) infections are increasingly rapidly worldwide. The reason for this phenomenon is unclear, but may include the ageing population, the increasing use of immunosuppressive drugs, the increasing prevalence of diseases that confer susceptibility to NTM, such as COPD and bronchiectasis, and growing testing for NTM. Awareness of the NTM related diseases is rising but is still suboptimal. Guidelines from the American Thoracic Society and Infectious Diseases Society of America have provided a framework for evaluating disease and evaluating care. Compliance with these guidelines is, however, very poor globally. NTM infections are amongst the most challenging cases that respiratory and infectious diseases physicians face. The challenges include intrinsic antibiotic resistance, complex drug regimens, poor tolerability and significant side effects associated with therapy and poor response rates. The decision to initiate treatment is therefore often difficult and requires careful evaluation of benefits and risks. Optimal management of NTM infections requires multidisciplinary care with close collaboration between physicians, microbiologists, physiotherapist/allied health professionals, primary care physicians and the patient. There remains a need for greater research into the epidemiology, clinical evaluation and treatment of NTM pulmonary disease. Randomised clinical trials are now being conducted which may provide useful data on the effectiveness of some new and existing therapies. In this review, we discuss the growing importance of NTM pulmonary disease and the opportunities for progress in clinical research for these conditions.