Our studies on the isotope effects in tunneling reactions are autoreviewed. Large isotope effects are observed in tunneling reactions, which take place by passing through the potential energy barrier for a reaction. A very large isotope effect more than 3×10 4 was obtained in tunneling reactions H(D)+H 2 (D 2) in γ-rays-irradiated solid hydrogen at 4.2 K, though there is no isotope effect in a hot atom reaction. The isotope effect on H 2 or D 2 detachment from a 2,3-dimethylbutane cation, produced by γ-radiolysis, amounts to a very large value of 1.7×10 4 at 77 K that indicates a tunneling detachment of a hydrogen molecule. The tunneling reaction of tritium atoms, produced by a 3 He(n, p)T reaction, with H 2 or D 2 in liquid helium at 1.3 K shows a large isotope effect of 150. A large isotope effect (20-50) was observed in the tunneling reaction of vitamin C and the long-lived protein radicals in biological systems. It is concluded that large isotope effects caused by a tunneling reaction play a role in radiation chemistry, a nuclear fusion technology and radiation biology.