Inflammatory Bowel Disease (IBD) comprising Ulcerative Colitis (UC) and Crohn’s Disease (CD) is debilitating chronic immune disorder of the intestinal mucosa, multigenic in nature, resulting from dysfunctional interactions between the intestinal immune system and its micro flora, influenced by host genetic susceptibility as suggested in linkage, epidemiologic, racial, familial aggregation and twin studies. It has led to the discovery of mutations in nucleotide- binding oligomerization domain containing protein 2 (NOD2) also known as caspase recruitment domain containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1) which located in chromosome 16q12 and associated with ileal CD, also numerous other genes’ mutations have been found to be associated with IBD susceptibility such as NOD1/CARD4 mutations in chromosome 7p14.3 in UC patients. Nod-like receptor family plays a key role in realization of innate and adaptive immune response. Their polymorphisms may shift balance between pro- and antiinflammatory cytokines, modulating the risk of chronic inflammation. The rational and prevalence of IBD is dependent on geographic location and racial background.