Inflammatory bowel disease (IBD) is comprised of both ulcerative colitis (UC) and Crohn's disease (CD) and is a chronic inflammatory disorder that results from a dysregulated immune response in genetically susceptible individuals. Data from genome-wide association studies (GWAS) have identified approximately 70 genetic loci that confer susceptibility to CD and over 30 loci that are associated with UC. These genetic loci guide the understanding of the molecular mechanisms of these gene products and reveal that alterations in the immune response underlie the pathophysiology of IBD. This review highlights critical areas in the microbiome, innate immune response, and the adaptive immune response that lead to the chronic mucosal inflammation typically seen in IBD.