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In assessing the best evidence for optimizing management of inflammatory bowel disease (IBD), the focus is typically on anti-inflammatory agents and therapies that modulate the immune system. The intestinal immune response remains the key focus of developing therapies as well. In the past decade, the concept of dysbiosis of the gut microbiome has emerged as a potential pathogenetic focus in IBD, and with this a burgeoning interest in manipulating the microbiome as a means of controlling the disease has emerged. In this review, anti-inflammatory, immune-modulating, and microbiome-modulating therapies will be covered in terms of what is known today, as well as treatments that may be part of the therapeutic armamentarium in the near future. Concurrent with the evolution of our understanding of the basic biology of IBD, there is an increasing appreciation for the disconnect between patients’ symptoms and inflammatory disease. As clinical trials have simultaneously addressed both symptom scores and mucosal healing, investigators and clinicians have gained a greater appreciation for the fact that many symptoms may not be driven by active inflammation, and hence focusing only on immunomodulatory therapies would not serve patients’ needs fully. Furthermore, there is an emerging recognition of the importance of stress and psychological health in symptom experience and treatment needs. In this review, approaches to managing patients’ symptoms as well as other adjunctive approaches to improving well-being will also be discussed. Finally, throughout this review, important research questions regarding different aspects of treatment will be proposed.