Advances in the understanding of inflammatory cascades and the role of cytokines and cell adhesion molecules in IBD pathogenesis has led to a therapeutic shift from general immunosuppressive therapy toward a more pathway-based approach. The identification of specific immunomodulatory molecules that possess defined pathogenic roles, such as pro-inflammatory cytokines, led to the advent of several anti-TNF monoclonal antibodies that have become the mainstay of IBD treatment. However, the utilization of these agents is often not maximized. Even among patients appropriately treated with anti-TNF agents, less than half achieve clinical remission and mucosal healing suggesting the involvement of other immunologic pathways. Thus, this session will focus on optimizing current biologic therapies, overcoming treatment challenges, the underlying mechanisms of IBD as treatment targets, and exploring how new and emerging therapies may facilitate a personalized approach to patient management.