Celiac disease (CD) is an intestinal disorder caused by intolerance to dietary gluten. HLA-DQ genes are the major risk factors for CD. In addition, non-HLA genetic factors might play a role in the development of the disease. The most common among the candidate genes, are those encoding for the cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and tumor necrosis factor α (TNFα). In order to test for the importance of these two genes in the etiology of CD in Jordanian celiac disease patients, we investigated the CTLA4 +49 A/G and TNFα –308 G/A polymorphisms in 85 patients, 100 healthy matched controls and 30 celiac families (56 members). Our results indicated that the frequency of the CTLA4 +49 GG genotypes and G allele were significantly higher in patients when compared with controls. This significant increase in the frequency of both, GG genotype and G allele, is also demonstrated in celiac disease families compared with the control group. On the other hand, no significant differences were found in TNFα–308G/A polymorphisms in celiac disease patients compared with controls. In addition, no significant differences, in the frequency, were found when the family group compared with control group for both AA genotype and A allele. Our results demonstrated the obvious role of the CTLA4+49 G allele in celiac disease development among Jordanian celiac patients and there is no association of TNFα–308A allele with CD patients in Jordan.