The probiotic Escherichia coli strain Nissle 1917 is in addition to some Lactobacilli sp. one of the best-studied probiotic strains. This particular E. coli strain was isolated in 1917 based on its potential to protect from presumably infectious gastroenteritis. Initial therapeutic success was noted in the management of gastrointestinal infectious disorders and infections affecting the urinary tract; the focus shifted later to chronic inflammatory conditions. The unique combination of fitness and survival factors to support intestinal survival, the lack of virulence, and obvious probiotic properties make this microorganism a safe and effective candidate in the treatment of chronic inflammatory bowel diseases. Three large clinical trials have assessed the potential in the maintenance of remission of ulcerative colitis and equivalence to standard 5-ASA medication was documented. This review aims to discuss important mechanisms of E. coli Nissle 1917 and will review the available literature regarding treatment of inflammatory bowel diseases.