Monoclonal antibody-based immunotherapy is a crucial component of cancer therapy. Advances in genetic engineering allowed for modifications that have boosted the efficacy of monoclonal antibodies (mAbs) and led to an explosion of new drugs in the last decade. The majority of leading edge mAbs approved since 2020 are for treatment of cancers that have failed to respond to the standard of care, and these newly approved mAbs allow for selective targeting of tumors for destruction and/or the promotion of immune responses. However, there are important considerations and limitations that must be considered when designing treatment strategies. This chapter briefly describes the history of mAbs; the mechanism, structure, and function of mAbs; recently approved mAbs and their functions; and challenges and considerations to using mAbs.