Background Adherence rates for chronic pediatric conditions are approximately 50%. The primary objective of the study was to assess rates of adherence using four different measurement methods for children with cystic fibrosis (CF). Methods Participants included 37 children with CF between 6 and 13 years of age and their primary caregivers. Adherence measures included parent and child self-reports, diary data, pharmacy refill history, and electronic monitors. Results Results suggested that rates of adherence varied by treatment component and across measurement methods. However, when examining more objective measures, rates of overall adherence were below 50% for children with CF, indicating generally poor adherence to the treatment regimen. For example, rates of adherence to enzyme medications, using electronic and diary measures, ranged from 27% to 46%. Conclusions The multi-method measurement approach provided unique information regarding rates of adherence for each disease condition by type of treatment component. Accurately measuring rates of treatment adherence for children with CF is an important step in developing effective interventions to influence these behaviors.