Stress may cause behavioral and/or psychiatric manifestations such as anxiety and depression and also impact on the function of different visceral organs, namely the gastrointestinal and cardiovascular systems. During the past years substantial progress has been made in the understanding of the underlying mechanisms recruited by stressors. Activation of the corticotropin-releasing factor (CRF) signaling system is recognized to be involved in a large number of stress-related behavioral and somatic disorders. This review will outline the present knowledge on the distribution of the CRF system (ligands and receptors) expressed in the brain and peripheral viscera and its relevance in stress-induced alterations of gastrointestinal and cardiovascular functions and the therapeutic potential of CRF(1) receptor antagonists.