The revised Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) quality of life (QoL) instrument has been updated and expanded to provide more complete and accurate coverage of human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-related QoL. Factor analysis and the Rasch measurement model were used to determine a new subscale structure for the FAHI. The content of these subscales, including physical well-being (ten items, alpha = 0.91), function and global well-being (13 items, alpha = 0.86), emotional well-being/living with HIV (10 items, alpha = 0.82), social well-being (eight items, alpha = 0.73), and cognitive functioning (three items; alpha = 0.75), reflect both general illness- and HIV/AIDS-specific QoL concerns: a total QoL score can also be calculated for the FAHI (44 items, alpha = 0.91). Psychometric evaluation revealed good internal consistency reliability for the FAHI and its subscales. In addition, construct validity, known groups validity and sensitivity to change were demonstrated by significant associations between the FAHI and additional indicators of functional status, psychological symptoms, stress and illness severity. In summary, the FAHI is a psychometrically sound instrument that captures multiple important dimensions of HIV/AIDS-related QoL. It is brief, easy to administer and score, has been translated into nine languages other than English and is appropriate for use in clinical trials and clinical practice.