Inflammatory Bowel Disease (IBD) with its two most common subforms, Crohn’s disease (CD) and Ulcerative colitis (UC), is a complex, chronic disease that is caused by a combination of genetic and environmental factors, with genetics accounting for 50-60% in CD. Genome-wide association studies (GWAS) and meta-analyses were very successful and have so far identified 163 susceptibility loci for IBD. Genotyping-based analyses, however, focus on known variants in the human genome and therefore exome and genome sequencing complements this approach as it allows for the detection of previously unknown and rare variants that may be involved in disease etiology. In this context, the Institute of Clinical Molecular Biology (IKMB) is involved in numerous sequencing projects for IBD. These involve sequencing of severe, early-onset cases with a potentially monogenic cause, concordant and discordant twin pairs and multiplex families with several affected individuals as well as cohorts of unrelated IBD cases to identify novel variants involved in the development of IBD.