Although the survival rate for systemic lupus erythematosus (SLE) has improved dramatically during the past 50 years, the quality of life of patients afflicted with this disease remains poor. Currently existent measures of disease activity and damage in SLE do not capture the patient's perspective and health-related quality of life (HRQoL). Most studies in SLE pertaining to HRQoL are from developed Western societies, with only a few from others. These studies have been conducted predominantly in women and using the Medical Outcomes Survey Short Form 36, a generic HRQoL instrument that has been shown not to be sensitive to change in lupus. Existent lupus-specific HRQoL measures have not yet been used in SLE clinical trials. New HRQoL research tools are currently undergoing validation in different countries, languages, and cultural settings, which may help dissect the underlying role of socioeconomic status and specific disease-related features that impact SLE-related quality of life.