This Practice Point commentary discusses the findings and limitations of a study by Welton et al. that assessed the effect of combined hormone replacement therapy (HRT) on health-related quality of life (QOL) in postmenopausal women. Evidence of the effect of HRT on health-related QOL in this group of patients in prior literature has been lacking, in part because of the varied, nonvalidated instruments used for evaluation. Welton et al. overcame that issue by the use of multiple questionnaires, and included specific questions on sexual functioning. However, all studies on health-related QOL are limited by the subjective selection of the parameters included in the instruments. Within this limitation, these authors concluded that HRT (estrogen alone in women without a uterus, and estrogen plus progestin for women with a uterus) offers more benefit than risk for postmenopausal, symptomatic women.