Distinguished researchers and clinicians review the biological and biomedical aspects of gasotransmitters, emphasizing signaling transduction mechanisms in general, and ion channel regulation in particular. The authors discuss the endogeneous metabolism and regulation of gasotransmitters, their toxicological profiles and biological actions, and their interactions in terms of their production and effects. The physiological roles of NO, CO, and H2S in the regulation of the cardiovascular, neuronal, and gastrointestinal systems, as well as of cell metabolism, are also reviewed, along with the interaction of the gastrotransmitters with KATP, KCa voltage-gated Ca2+, voltage-gated Na+, and cyclic nucleotide-gated ion channels.