Crohn's disease is associated with substantially impaired health-related quality of life (HRQoL). Even in the absence of active disease, patients with Crohn's disease report lower HRQoL, poorer function, and greater concerns, than those without disease. Achievement of disease remission in Crohn's disease, whether by pharmacological or surgical means, is associated with improved HRQoL, although the durability of the improvement seen after intestinal resection is uncertain because of the high rate of postoperative disease recurrence. This review focuses on the available literature on HRQoL in patients with Crohn's disease with an emphasis on the effects of intestinal resection and immunomodulatory therapy.