Background Adherence to CF treatments is poor, which can lead to negative health outcomes. The objective of our study was to qualitatively investigate the barriers and facilitators of self-management among older adolescents and adults with CF. Methods Individual semi-structured interviews were conducted, audio-taped, transcribed verbatim and coded to identify common themes. Results Twenty-five patients were interviewed. Four broad themes were identified: Barriers to Self-Management (e.g., treatment burden (identified by 64% of patients), accidental or purposeful forgetting (60%), no perceived benefit (56%)), Facilitators of Self-Management (e.g., CF clinic visits (76%), social support (68%), perceived benefit (68%)), Substitution of Alternative Approaches to Conventional Management (36%) and Planned Non-adherence (32%). Conclusions Older adolescents and adults with CF identified many barriers and facilitators of adherence that may be amenable to self-management counseling strategies, particularly the use of health feedback.