Health-related quality of life (HRQoL) is a domain of quality-of-life assessment that is influenced by the individual's perception of his or her health status. Measurement of HRQoL can enable physicians to understand how an illness interferes with a patient's day-to-day life, improve patient-physician communication, and optimize clinical outcomes. Chronic rhinosinusitis (CRS) is one of the most common chronic diseases, affecting 14-16% of the adult US population. In addition to significant health care costs, CRS has been shown to substantially reduce HRQoL. In this review article, we discuss the definition and interpretation of HRQoL data and describe several validated rhinosinusitis HRQoL instruments. Additionally, we review how CRS functions to lower HRQoL and the effect of medical and surgical intervention on improving HRQoL status. By understanding the relationship between CRS and associated chronic conditions, clinicians can target their evaluation to problems that will maximize clinical success.