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Carbon monoxide (CO) is a ubiquitous gaseous molecule produced in mammals that functions as a signaling mediator in the control of a variety of cellular and physiological processes. By virtue of its chemical structure, CO preferentially binds to transition metal centers, which in the cell are mainly represented by the ferrous iron contained in hemoproteins. In this chapter, we postulate that hemoproteins are the primary targets that transduce the signal of CO, initiating a cascade of events that may explain the contribution of CO to the regulation of vascular tone, cell proliferation and apoptosis, neurotransmission, redox signaling, and inflammation. In addition, a new emerging role for CO in the modulation of energetic metabolism is described, particularly concerning its interaction with mitochondria.

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