Owing to their ability in destroying or slowing down the growth of bacteria, antibiotics have been widely used to treat the bacterial infections. However, because of the long-term and irresponsible use of antibiotics, resistance to antibiotics has become a serious problem directly threatening the public health worldwide. To fight against and resist β- lactam antibiotics, bacteria usually employed β-lactamases, especially the metallo-β-lactamases, to hydrolyze the C-N bond of the β-lactam ring so as to inactivate the antibiotics. In this minireview, we are to summarize the structural features of the metallo-β-lactamases, as well as their antibiotic binding modes and resistance mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to overcome the resistance problem and find novel inhibitors against the metallo-β-lactamases.