The assessment of health-related quality of life (HRQOL) plays an increasingly important role in the evaluation of therapeutic interventions in various chronic diseases, including inflammatory bowel disease (IBD). There are three main types of HRQOL instruments, each of which have specific strengths and limitations. Global assessments provide a general impression of the patient's HRQOL, but they do not identify specific domains of dysfunction. Generic instruments can be used to show similarities or differences among groups or populations, but they may not be sensitive to changes over time or after treatment in groups of patients with specific diseases. Disease-specific instruments, which are derived from and validated in particular disease groups, are the most sensitive indicators of change in HRQOL over time or with treatment. There are several potential sources of bias in HRQOL measurement, and certain instruments are more or less sensitive and reliable than others in detecting impaired function in patients with IBD. Despite differences between studies regarding specific HRQOL findings, as a group, these assessments confirm that HRQOL can be impaired significantly in patients with IBD. Reliable validated HRQOL instruments should be applied with the same methodological rigor as other assessments in clinical trials of different therapeutic strategies for patients with IBD.