Airway clearance therapy (ACT) requires a substantial time, effort and resource commitment on the part of families and patients with cystic fibrosis (CF). Lack of compliance with caregiver recommendations and adherence to a proposed therapeutic plan occurs more than 50% of the time with ACT and is particularly common in adolescents. There is a large menu of ACT devices and techniques from which to choose. Increasing adherence and compliance requires an effort on the part of the CF team, including regular visits to the CF center, matching the patient to the device or technique based on lifestyle and disease severity, selecting appropriate outcome measures and monitoring adherence and compliance. Successful ACT also requires the CF team to understand individual patient situations, individualize ACT programs and accept a realistic level of patient participation.