An antibody-drug conjugate consists of a potent cytotoxic drug attached to a monoclonal antibody specially targeted on cancer associated antigen. The antigen targeted chemotherapy can improve therapeutic index by increasing potential efficacy and decreasing systemic toxicity. In this review, we described the study and the progress in antibody engineering, the process of drug selection, and the development of linker to optimize the clinical trials. We also discussed about the possible mechanism of cell death induced by an antibody- drug conjugate and the potential resistance to an antibody-drug conjugate. Nonetheless, the successful results from Gentuzumab ozogamicin and other encouraging clinical trials will continue to drive the preclinical development of antibody-drug conjugates.