Antibiotic treatment of pulmonary disease caused by NTM is based on a combination of antimycobacterial drugs. These drugs should be chosen according to the species involved. Evidence from prospective clin. trials is variable. In vitro susceptibility tests have not been validated, but are increasingly being recognized as a plausible potential aid to help combat diseases caused by difficult-to-treat NTM species, particularly in the case of treatment failure. In this chapter, the author seeks to explore areas of controversy and to challenge conventional thinking in the management of NTM pulmonary disease.