Molecular hydrogen is at the forefront of biomedical research for its remarkable therapeutic potential.Over 400 scientific articles suggest molecular hydrogen to be therapeutic in essentially every organ of the human body and in 150 different human,animal and plant disease models.Many of these benefits are mediated by non-radical scavenging activities, suggesting that molecular hydrogen is a novel gaseous signal modulator.Although the actual underlying molecular mechanisms and primary targets of hydrogen remain elusive, the evidence that hydrogen exerts biological effects in eukaryotes is well established.These biological effects are surprising and difficult to believe, but from an evolutionary perspective they are somewhat predictive.Eukaryotes have been exposed to molecular hydrogen since their origins.Hydrogen is considered the father of all the elements and was intimately involved in the genesis and evolution of life(e.g.hydrogenases, mitochondria).Over the millions of years of evolution,plants and animals have developed a mutualistic relationship with hydrogen-producing bacteria resulting in basal levels of molecular hydrogen in eukaryotic systems.The constant exposure to molecular hydrogen may have conserved the original targets of hydrogen, as can be extrapolated by genetic remnants of hydrogenase enzymes in higher eukaryotes.Alternatively, but not exclusively, eukaryotes may have developed sensitivity to molecular hydrogen over the millions of years of evolution.This evolutionary perspective may help explain why molecular hydrogen exerts a physiological effect inbiological systems.