Carbon monoxide (CO) is produced endogenously in the body as a byproduct of heme degradation catalyzed by the action of heme oxygenase (HO) enzymes. An inducible form, HO-1, responds to many factors such as oxidative stress, hypoxia, heme, bacterial endotoxins, proinflammatory cytokines and heavy metals. HO-2 is constitutively expressed under basal conditions in most human tissues including brain and gonads. Recent data show that CO is a gaseous mediator with multidirectional biological activity. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. CO shares many properties with another established vasodilatator and neurotransmitter - nitric oxide (NO). Both CO and NO are involved in neural transmission, modulation of blood vessel function and inhibition of platelet aggregation. The binding to guanylate cyclase, stimulation of the production of cGMP, activation of Ca2+-dependent potassium channels and stimulation of mitogen-activated protein kinases are well known cellular targets of CO action. Since CO is nowadays a subject of extensive investigation in many centers worldwide, the aim of the present study was to present the role of CO in various aspects of human physiology with special focus on its activity in the gastrointestinal tract.