This study sought to identify multidimensional factors of life satisfaction in individuals with HIV through a factor analysis of the Quality of Life Inventory (QOLI), and to examine the relationship of these factors to health-related quality of life, depression, and medication adherence. Four quality of life domains emerged: Achievement, Self-Expression, Environment, and Interpersonal Relationships. QOLI means were substantially lower than the normative means and were significantly related to the SF-12 mental (but not the physical) component summary. Multidimensional assessments of quality of life in HIV may help specify targets sensitive to psychosocial interventions.