Therapeutic compounds interfering with T cell trafficking are a new column of inflammatory bowel disease (IBD) treatment. Currently, the anti-α4β7 integrin antibody vedolizumab is successfully used in the clinic and further drugs are likely to follow. Despite these clinical advances, the precise mechanistic background of their action is only gradually elucidated and still a matter of intensive research. Only recently, advances made with the help of new in vivo models and human studies have contributed to shape our concept of T cell trafficking in IBD by deciphering some important and so far unanswered questions. At the same time, basic and clinical data have generated new issues to be addressed on the way toward a clear perception of trafficking mechanisms and toward elucidation of the action of compounds interfering with this process. In this review, we will give a comprehensive outline of all components of T cell trafficking in regard to IBD before discussing the current knowledge concerning targeted interference with integrins in this complex network. Moreover, we will summarize remaining ambiguity and give an outlook on potential future targets.