Stress has long been postulated to influence the progression of inflammatory bowel disease (IBD). Our current understanding of the relationship between stress and IBD is still limited, and hence explanation for the occurrence of relapses has remained largely speculative. Stress affects the immune system, the neuroendocrine system and the intestinal epithelia. Stress induces the release of pro-inflammatory Th1 cytokines and neuropeptides, such as tachykinins. Thereby, stress may induce alterations of the intestinal epithelium via the interaction of the neuroendocrine and immune system and may induce relapses of IBD. The present review focuses on this network and highlights the role of distinct mediators and mechanisms, i.e. neurotransmitters, hormones and immune cells, which are involved in the response to stress on the one hand, and contribute to the onset, progression or relapses of IBD on the other.