Carbon monoxide (CO) and hydrogen sulfide (H2 S) used to be thought of simply as lethal and (for H2 S) smelly gaseous molecules; now they are known to have important signaling functions in the gastrointestinal tract. CO and H2 S, which are produced in the gastrointestinal tract by different enzymes, regulate smooth muscle membrane potential and tone, transmit signals from enteric nerves, and can regulate the immune system. The pathways that produce nitric oxide, H2 S, and CO interact; each can inhibit and potentiate the level and activity of the other. However, there are significant differences between these molecules, such as in half-lives; CO is more stable and therefore able to have effects distal to the site of production, whereas nitric oxide and H2 S are short lived and act only close to sites of production. We review their signaling functions in the luminal gastrointestinal tract and discuss how their pathways interact. We also describe other physiological functions of CO and H2 S and how they might be used as therapeutic agents.