Celiac disease is a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. The majority of patients responds to a gluten-free diet but a small number do not. After the exclusion of gluten in the diet, ulcerative jejunititis, and an enteropathy-associated T-cell lymphoma, another treatment modalities, such as systemic steroids and immunosuppressives, may be necessary. This article reports the case of a 47-year-old white woman with immunoglobulin A deficiency. She was diagnosed with celiac disease with subtotal villous atrophy on jejunal biopsy together with positive antiendomysium and antigliadin immunoglobulin G antibodies. Despite close adherence to a gluten-free diet, her weight continued to decrease, she had diarrhea, and her distal duodenal histology showed no improvement. Some improvement in her symptoms was observed with cyclosporine and systemic steroids, but this was not sustained. Recent evidence has suggested that anti-tumor necrosis factor alpha antibodies have a role in the amelioration of an animal model of villous atrophy, and after careful consideration, she was treated with infliximab. There was a dramatic improvement in her weight, symptoms, and distal duodenal histology. The response has been maintained for 18 months while on azathioprine therapy. It is concluded that infliximab is an effective treatment that may be considered in a small number of patients with refractory celiac disease, resistant to other therapy.