Due to the coming energy crisis, economical production of hydrogen that is the next-generation clean fuel is an urgent task for chemists. In this article, we are going to discuss some examples of hydrogen activation by metal complexes or metal-free compounds as well as bioinorganic synthetic methods to hydrogenases mimics. Hydrogenases not only can convert hydrogen to protons and electrons but also reduce protons to hydrogen in a highly efficient manner. By learning from mother nature, inspiration by hydrogenases may prompt chemists to develop advanced models.