Health-related quality of life (HRQL) has been assessed in various lung transplantation (LT) investigations but never analyzed systematically across multiple studies. We addressed this knowledge gap through a systematic literature review. We searched the PubMed, CINAHL and PsychInfo databases for publications from January 1, 1983 to December 31, 2011. We performed a thematic analysis of published studies of HRQL in LT. Using a comparative, consensus-based approach, we identified themes that consistently emerged from the data, classifying each study according to primary and secondary thematic categories as well as by study design. Of 749 publications initially identified, 73 remained after exclusions. Seven core themes emerged: (1) Determinants of HRQL; (2) Psychosocial factors in HRQL; (3) Pre- and posttransplant HRQL comparisons; (4) Long-term longitudinal HRQL studies; (5) HRQL effects of therapies and interventions; (6) HRQL instrument validation and methodology; (7) HRQL prediction of clinical outcomes. Overall, LT significantly and substantially improves HRQL, predominantly in domains related to physical health and functioning. The existing literature demonstrates substantial heterogeneity in methodology and approach; relatively few studies assessed HRQL longitudinally within the same persons. Opportunity for future study lies in validating existing and potential novel HRQL instruments and further elucidating the determinants of HRQL through longitudinal multidimensional investigation.