Measurement of health-related quality of life (HRQL) is becoming an increasingly important endpoint to researchers and clinicians. In the context of upper gastrointestinal disorders, understanding the impact of the symptoms and their treatments on physical, psychological, and emotional well-being is crucial. The objective of this review is to provide a background for HRQL assessment for patients with upper GI disease. We assess and critique available generic and disease-specific HRQL instruments, and specify the factors that should be considered when evaluating an instrument. If employed correctly, HRQL assessments for patients with upper GI disease could improve quality of care.