In recent years, interest in anti-cancer therapeutic monoclonal antibodies (mAb) has been renewed. Several of these reagents have been approved for therapy in a variety of cancer patients and many others are in different stages of development. It is believed that multiple mechanisms are involved in the anti-cancer effects of these reagents. However, several in vitro and in vivo studies have demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) is their predominant mode of action against cancer cells. The requirement for a direct interaction between mAb and receptors for the Fc region of the antibodies (FcR) has been demonstrated for anti-tumor effects of these antibodies. Consequently, FcR-bearing immune effector cells play an important role in mediating their effects. It is not surprising that cancer cells have developed different strategies to evade these antibodies. Several strategies are proposed to potentiate the mAb-mediated ADCC in cancer patients. They may enhance anti-cancer therapeutic effects of these regents.