Quality of life (QoL) is vitally important to patients with chronic illnesses such as ulcerative colitis (UC) and has been assessed in observational, cross-sectional, and cohort studies. However, relatively few clinical trials have evaluated the QoL of patients with UC. Recently, greater availability of the necessary tools has facilitated the undertaking of studies showing that QoL of patients with UC is reduced significantly compared with that of the general population. Studies using disease-specific instruments have identified disease severity as the strongest predictor of QoL, with other disease-related predictors including type of medical or surgical treatment and the efficacy, tolerability, and acceptability to patients of particular types of medical or surgical treatments. Other factors, such as comorbid medical or psychosocial problems and adherence to treatment, also affect QoL. Combined use of generic and disease-specific instruments in clinical trials can ensure that all clinically relevant unexpected events (generic instrument) and important improvement or deterioration (disease-specific instrument) are captured. For accurate outcomes assessment, the use of comprehensively validated instruments is critical. The need for the development and evaluation of new instruments will be determined by the mechanisms and targets of novel therapies. Ultimately, QoL assessment of effective therapies will play a strong role in pharmacoeconomic evaluations, providing health policy makers with the evidence to support the treatments that can most effectively normalize QoL through complete symptom resolution, minimal side effects, and convenient administration.