OBJECTIVES: The impact of MDD on HRQOL is well documented, but little information exists about commonly used HRQoL instruments’ adherence to EMA requirements for psychometric properties and content relevance. This work examines commonly used HRoQL instruments for their relevance to MDD, based on their content, concepts measured and psychometric properties, and use in published MDD studies. METHODS: A qualitative research paper provided a conceptual model for MDD (1). The SF-36 Health Survey (SF-36), Sheehan Disability Scale (SDS), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Health Status Questionnaire-12 (HSQ-12) and EuroQol (EQ-5D) were mapped to this conceptual model to examine their relevance to MDD. The measures’ reliability, validity, responsiveness to change in depression and use in MDD trials and labelling were examined through review of classic databases (including: PROQOLID, PROLABEL, MEDLINE, PSYCHINFO, FDA, EMA). Where no information on MDD was available, data for mood disorders were explored. RESULTS: The SF-36, SDS, Q-LES-Q and EQ-5D have been widely used in MDD, with SDS and Q-LES-Q results included as part of approved EMA labelling claims in mood disorder indications. These instruments are clinically well established and the combination covers HRQoL concepts relevant to the MDD population [emotional/social/physical (specifically bodily pain)]; Q-LES-Q and SF-36 are the most comprehensive HRQoL measures. All instruments met EMA psychometric requirements for validity, reliability and responsiveness to changes in depressive symptoms and in elderly populations for the HSQ-12. Furthermore, the instruments have been linguistically validated for use in many countries. CONCLUSIONS: These commonly used instruments are relevant to MDD and meet EMA criteria for reliability, validity and responsiveness. Thus, we conclude that these instruments are appropriate for use in clinical programmes to assess the impact of MDD treatment on HRQoL and overall functioning, particularly to support claims in Europe.