Inflammatory bowel diseases (IBD) are idiopathic chronic inflammations: the etiology of Crohn's disease (CD) and ulcerative colitis (UC) is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms trigger an event, leading to the activation of an intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Considering these aspects, medical management of inflammatory bowel disease has changed considerably over the past decade. Advances in biotechnology has allowed for the introduction of many biologic therapies, other than anti-TNF therapies. Many of these drugs showed clinical benefit for induction and maintenance therapy, both in UC and CD. Although numerous, at present only monoclonal anti-TNF antibodies are currently available worldwide. Other biological agents have been tested or are under evaluation. This paper systematically reviews the mechanism-of-action, efficacy, short-term and, where available, long-term safety of biological agents that have been approved for the treatment of IBD or are under evaluation which target different molecules other than tumor necrosis factor alpha (TNF-alpha).