The Medical Outcomes Study HIV Health Survey (MOS-HIV) is a brief, comprehensive measure of health-related quality of life (HRQoL) used extensively in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The 35-item questionnaire includes ten dimensions (health perceptions, pain, physical, role, social and cognitive functioning, mental health, energy, health distress and quality of life (QoL) and takes approximately 5 minutes to complete. Subscales are scored on a 0-100 scale (a higher score indicates better health) and physical and mental health summary scores can be generated. The MOS-HIV has been shown to be internally consistent, correlate with concurrent measures of health, discriminate between distinct groups, predict future outcomes and be responsive to changes over time. Limited experience suggests acceptable reliability and validity in women, injecting drug users and African-American and lower socioeconomic status patients. The MOS-HIV is available in 14 languages and has been included as a secondary outcome measure in numerous clinical trials for all stages of disease. In several studies it has detected significant differences between treatments; in some cases concordant with conventional endpoints and, in others, discordant. The interpretation of scores is facilitated by an explanation in terms meaningful to the intended audience. Research is needed to compare the MOS-HIV to other strategies for HRQoL assessment in early HIV disease.