Molecular hydrogen (H-2) was believed to be inert and nonfunctional in mammalian cells. We overturned this concept by demonstrating that H-2 reacts with highly reactive oxidants such as hydroxyl radical ((OH)-O-center dot) and peroxynitrite (ONOO-) inside cells. H-2 has several advantages exhibiting marked effects for medical applications: it is mild enough neither to disturb metabolic redox reactions nor to affect signaling by reactive oxygen species. Therefore, it should have no or little adverse effects. H-2 can be monitored with an H-2-specific electrode or by gas chromatography. H-2 rapidly diffuses into tissues and cells to exhibit efficient effects. Thus, we proposed the potential of H-2 for preventive and therapeutic applications. There are several methods to ingest or consume H-2: inhaling H-2 gas, drinking H-2-dissolved water (H-2-water), injecting H-2-dissolved saline (H-2-saline), taking an H-2 bath, or dropping H-2-saline onto the eyes. Recent publications revealed that, in addition to the direct neutralization of highly reactive oxidants, H-2 indirectly reduces oxidative stress by regulating the expression of various genes. Moreover, by regulating gene expression, H-2 functions as an anti-inflammatory, antiallergic, and anti-apoptotic molecule, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under way. Since most drugs specifically act on their specific targets, H-2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H-2 has potential for clinical applications for many diseases.