Bacteriophage is one of the most abundant and long­standing individuals in the biosphere of the earth. Bacteriophage is also one of the most characteristic candidates to deal with antibiotic resistant bacterial infections. In this paper, we discussed the phage­resistance mechanism of bacteria and bacteriophages’ responses from the aspects of bacteria and phages interactions, such as inhibition of the bacteriophage adsorption, super infection exclusion, restriction modification system, CRISPR­Cas, and abortive infection.