The development and application of culture-independent approaches (i.e. high throughput sequencing of bacterial and viral community DNA) has generated a profound shift in our understanding of chronic respiratory infections in cystic fibrosis (CF) patients. We now recognize the importance of polymicrobial interactions, environmental conditions and evolutionary adaptations in the progression of CF disease. Yet, a lack of ecological perspective has limited the translation of bench research into effective therapeutic strategies. For example, how do you describe the response of a bacterial community to an environmental condition, without direct measurements of these conditions in vivo? Recently, applications of integrated ‘omics’ approaches – genomics, transcriptomics, proteomics, and metabolomic profiling – have shed light on the ecological dynamics of CF bacterial communities, though many outstanding questions remain. This will be the 4th bi-annual meeting of the TSRC CF workshop, which began in 2009 with the goal of building theoretical models of CF lung physiology to identify ecological and evolutionary instabilities. We will explore ecological and evolutionary approaches to modeling the CF lung environment and the microbiota that resides there, with the ultimate goal of devising more effective clinical therapy. In addition to a review of the last few TSRC CF meetings, talks from both basic scientists and clinicians will emphasize new tools and hypotheses about the CF bacterial ecosystem and its relation to disease progression. But as with all good Telluride workshops, the aim is to do research on-site. One-hour talks have been known to last an entire afternoon due to intensive probing from the audience. Come prepared to give chalk talks and/or show slides and plots about your work… anything that you feel is important!