An unmet medical need exists for novel targeted therapies for inflammatory bowel disease (IBD) as many patients experience inadequate responses to antibody-based biologics. An oral drug formulation with reduced production costs and redundancy for healthcare staff to administer therapy ideally should result in diminished healthcare expenses and improved patient compliance. A new drug class of small molecules, the Janus kinase (JAK) inhibitors (jakinibs), fulfills these criteria and has recently shown efficacy in IBD. Here we provide an overview of the mode of action of jakinibs and provide a comprehensive overview of existing clinical studies. Convincing clinical data show that a complex cytokine-driven inflammation can efficiently be modulated by therapeutic inhibition of the JAK proteins.