There is no doubt that patients with immune-mediated inflammatory diseases (IMID) have a significantly impaired quality of life (QOL). Pain and disability often leave these patients helpless and frustrated. The recognition that addressing physical and psychological functioning plays a significant role in an overall treatment approach led to the inclusion of QOL measures as secondary outcomes in clinical trials with IMID patients. To that end, both generic and disease-specific instruments have been utilized. Measurement of health-related QOL (HRQOL) and patient-reported outcomes (PRO) in a controlled manner allows for better understanding of the correlation between different aspects of disease activity and QOL. In addition, the effects of different therapeutic options on HRQOL-related outcomes can be further evaluated. This 3-part section describes key QOL-related complaints of patients with IMID affecting joints, skin, or gut. An overview of the strengths and weaknesses of various commonly used HRQOL instruments is provided. Finally, the influence of anti-tumor necrosis factor-α agents on HRQOL outcomes, as assessed in recent clinical trials, is highlighted.