Crohn's disease (CD) is associated with a substantial healthcare burden that affects the patient, healthcare systems and society in general. To provide a systematic evaluation of published data relating to the economic and health-related quality-of-life (HRQoL) burden of CD in selected European countries (Germany, France, UK, Italy, Spain) and the USA since 2000. We undertook a systematic review of publications relating to CD, its economic burden and impact on HRQoL. Research questions focused on the disease costs from a societal perspective and HRQoL burden in adults and pediatric/adolescent patients according to disease stage/severity. Total, direct and indirect costs were identified, as well as the impact of CD on HRQoL measured using both generic and disease-specific instruments. Overall, 61 publications met the research criteria (38 on costs, 23 on HRQoL). CD in the USA and Europe together was associated with annual total costs of nearly a,not sign30 billion, more than half due to indirect costs. HRQoL was consistently and statistically significantly lower among CD patients compared with normal populations, due to physical, emotional and social effects. CD is a global health problem with high societal costs and substantial HRQoL burden. High-value care pathways including cost-effective therapies will help to induce and maintain remission, reduce complications of disease and improve HRQoL.