Nitric oxide (NO), carbon monoxide, and hydrogen sulfide in addition to hydrogen are well established as gaseous signal molecules throughout the body. Although the role of gasotransmitters in acute pancreatitis (AP) has been explored for many years, many details remain to be elucidated. The physiologic effect of NO in AP mainly relies on induced NO synthase, which stimulates the production of cytokines in the blood. Carbon monoxide inhibits nuclear factor-κB activation, which leads to amelioration of the inflammatory response. Hydrogen sulfide displays a dual role in the mechanism of AP according to its concentration in the system. Hydrogen is a newly discovered gaseous signaling molecule, and currently, there is little evidence that it has any function in alleviating inflammation. We discovered that hyperbaric oxygen is a novel gasotransmitter that has potential use in the treatment of AP. The correlation among hyperbaric oxygen, hypoxia inducible factor 1α, and other signaling pathways should be further studied. We also discuss some prospects and issues that remain to be resolved in this review. In summary, the discovery of gaseous signal molecules has established a new platform for deep investigation of the mechanism of AP, and our knowledge of the role of gasotransmitters in AP will increase with further research.