OBJECTIVES: To critically review available instruments for assessing quality of life (QoL) and health-related QoL (HRQL) in HIV and AIDS, with specific reference to suitability for clinical trials. METHODS: Literature searches were conducted using Medline, AIDSLine and PsycINFO to identify instruments used to measure QoL or HRQL in HIV and/or AIDS since 1990. Relevant literature pertaining to such measures was critically reviewed. Instruments were appraised according to the following issues: development (theoretical basis, content derivation); psychometric properties (dimensionality, test-retest reliability, internal consistency, face/content validity, construct validity, responsiveness); practicality for clinical trials (length, complexity, method/ease of administration and scoring); cultural considerations (language availability, cross-cultural validity, translation/adaptation methodology); and application in HIV/AIDS populations (study type, sample characteristics). RESULTS: Sixteen instruments were selected for review; 5 HIV/AIDS-specific (HAT-QoL, MQoL-HIV, LWHIV, HIV-QL31, FQLS), 3 adaptations of cancer-specific instruments (HOPES, FAHI, QLQ-C30 + HIV Module), 3 adaptations of generic instruments (MOS-HIV, HIV-PARSE, AIDS-HAQ), and the 5 most commonly employed generic instruments in HIV/AIDS (SF-36, SF-20, QWB, EQ-5D, QL-Index). Overall, the conceptual quality of the instruments reviewed was poor, with most lacking a theoretical model of the intended construct. As such, none of the instruments measure QoL, with most assessing the various dimensions of HRQL. The content of most of the instruments was derived without reference to patients with HIV/AIDS and, thus, would have limited applicability to this patient group. The HAT-QoL, MQoL-HIV and FAHI comprised items that appeared better targeted to the issues of relevance to patients with HIV or AIDS. However, the psychometric properties of the HAT-QoL and MQoL-HIV were poor. CONCLUSIONS: Of the instruments reviewed, the FAHI appears to be the most appropriate instrument for measuring HRQL in clinical trials. However, a number of its properties have yet to be adequately assessed (including face/content validity, test-retest reliability and unidimensionality of its scales).