Bacteriophage is the virus that infects bacteria. To resist bacteriophage infections, bacteria have evolved various antiviral mechanisms, which significantly promote the development of gene editing and lay down foundations for bacteriophage treatment. This review briefly concludes the molecular resistance mechanisms of host bacteria against bacteriophage infection. Next, the effects of such defense systems on bacteria physiology and ecology are discussed. Then, we summarized the limitations and future directions of bacteriophage resistance research.