A decade of rapid technological advances has provided an exciting opportunity to incorporate information relating to a range of potentially important disease determinants in the clinical decision-making process. Access to highly detailed data will enable respiratory medicine to evolve from one-size-fits-all models of care, which are associated with variable clinical effectiveness and high rates of side-effects, to precision approaches, where treatment is tailored to individual patients. The human microbiome has increasingly been recognised as playing an important part in determining disease course and response to treatment. Its inclusion in precision models of respiratory medicine, therefore, is essential. Analysis of the microbiome provides an opportunity to develop novel prognostic markers for airways disease, improve definition of clinical phenotypes, develop additional guidance to aid treatment selection, and increase the accuracy of indicators of treatment effect. In this Review we propose that collaboration between researchers and clinicians is needed if respiratory medicine is to replicate the successes of precision medicine seen in other clinical specialties.