OBJECTIVES: To review and evaluate available QOL instruments in MDS, the QOL burden of MDS, disease characteristics that influence QOL outcomes, and to provide recommendations for future research. METHODS: A systematic literature review was performed to identify QOL studies performed in MDS patients and published in English from 1995 to 2005. RESULTS: 53 abstracts were located; 13 studies were selected for review. The FACT-An, EORTC QLQ-C30, Quality of Life–E (QOL-E), and SF-36 all demonstrated acceptable validity in MDS patients. The FACT-An, QOL-E, and SF-36 had good internal consistency with Cronbach's alpha coefficients for subscales ranging from 0.92 to 0.94, 0.72 to 0.88, and 0.75 to 0.94, respectively. The FACT-An and EORTC QLQ-C30 showed appropriate responsiveness to change in prospective randomized trials. Two studies compared QOL among MDS patients with the general population. Statistically significantly (p<0.05) worse QOL was observed in the following domains: fatigue, physical functioning, role physical, vitality, social functioning, emotional functioning, and global health. Cognitive functioning was least affected. No study stratified QOL differences by MDS disease sub-group categories or International Prognostic Scoring System (IPSS) risk scores. However, four studies established a link between transfusion independence and better QOL. All studies found QOL to be significantly (p<0.05) better in transfusion-independent patients, even after controlling for haemoglobin level. Six studies found improvements in clinical status were associated with improved QOL. Changes in overall QOL were mostly linked to improvements in the fatigue, dyspnea, physical, and social functioning QOL sub-scales. CONCLUSIONS: MDS leads to significant QOL burden compared to similarly aged adults in the general population. QOL is an important endpoint in MDS research. Several validated instruments are available. Evidence on the clear link between transfusion dependency and impaired QOL suggests a potentially important role for new treatments that achieve higher transfusion independence among MDS patients.