OBJECTIVES: To systematically review published literature assessing the economic evidence of biologic treatments indicated for Crohn’s disease (CD). METHODS: Published articles between January 1995 and June 2011 were searched in PubMed, EMBASE, ABI/INFORM, Tuft’s Cost-Effectiveness Analysis Registry Database, Cochrane National Health Service Economic Evaluation Database, International Pharmaceutical Abstracts, Web of Science, and Google Scholar. Studies of interest included: 1) cost studies; 2) economic evaluations; or 3) narrative or systematic reviews related to economic evaluations of biological treatments used for moderate-to-severe CD. Exclusion criteria included the following characteristics: 1) CD-related cost studies that were narrative or systematic reviews; 2) CD-related cost studies that did not include costs of biologic treatments; 3) studies published only as abstracts; or 4) non-English studies. The primary outcomes of interest included costs associated with biological treatments and cost-effectiveness measures including incremental cost-effectiveness ratios. A threshold value of $50,000/QALY or £30,000/QALY was used to judge treatment cost-effectiveness. RESULTS: Twenty-nine studies were identified, including 12 economic evaluations and 17 cost studies or reviews of economic evaluations. Economic evaluation studies illustrated that infliximab was cost-effective compared with standard care for luminal CD when provided as induction therapy followed by: 1) episodic therapy over 5 or more years, or 2) maintenance therapy over one year. Additionally, adalimumab was found to be more cost-effective than both infliximab and standard care for luminal CD in terms of 1-year maintenance treatment with or without prior induction treatment. Cost studies revealed that infliximab usage reduced overall healthcare resource utilization and cost. Older reviews were inconclusive on the cost-effectiveness of biologic treatments used for CD. CONCLUSIONS: Limited evidence suggests that biologic treatments are cost-effective for CD under certain clinical situations. Future studies are recommended to include all indicated biologic treatments to provide a systematic comparison regarding their comparative benefits and costs.