OBJECTIVES: Cystic Fibrosis (CF) is a life-limiting, genetic disorder that has a tremendous impact on patient’s quality of life (QoL). The goal of this review is to summarize QoL literature in CF and identify instruments utilized to capture QoL data in adult patients. METHODS: A comprehensive literature search using PRISMA guidelines was conducted from January 2010 to October 2014 using electronic databases such as PubMed, Scopus, CINAHL, and Cochrane Reviews. Studies assessing physical, psychological, social and spiritual impact on patients with CF were identified. The QoL instruments from the studies were identified and a review of their psychometric properties in CF was conducted. The search strategy was limited to studies conducted in adult population. Full-text, published articles in the United States and Europe were included in the final review. RESULTS: A total of 14 QoL studies in CF which utilized 6 validated instruments were identified.  Three instruments were disease-specific (CFQ-R, CF-QOL, and a single item measure) and the remaining three were generic instruments (SF-36, EQ-5D, and UK-SIP).  CFQ-R was used in 11 studies, whereas 3 studies used the CF-QoL. Some important factors that influenced QoL in CF were pain, lung function, self-esteem, and ethnicity. Psychometric validation included validity (discriminant, convergent, and concurrent validity) and reliability testing. Reliability of the instruments was found to be within appropriate ranges (CFQ-R: Cronbach’s alpha ≥ 0.70; CF-QOL: Test-Retest >0.8; and Generic instruments: Internal Consistency >0.8).  CONCLUSIONS: Clinical outcomes, patient perception, and demographic variables were found to influence QoL in adult CF patients. CFQ-R is the most commonly reported QoL instrument in CF. Also, the time constraint physicians face in using QoL assessment in clinical practice can be addressed by the recently developed single-item, CF-specific QoL questionnaire.  Overall, CF has a negative impact on the physical, mental, and social aspects of patient’s life.