Bispecific antibodies (BsAbs), which target two antigens or epitopes, incorporate the specificities and properties of two distinct monoclonal antibodies (mAbs) into a single molecule. As such, BsAbs can elicit synergistic activities and provide the capacity for enhanced therapeutic efficacy and/or safety compared to what can be achieved with conventional monospecific IgGs. There are many building block formats to generate BsAbs and Trispecific antibodies (TsAbs) based on combining the antigen recognition domains of monoclonal antibodies (mAbs). This review describes the many and varied antibody-based building blocks used to achieve multivalency and multispecificity. These diverse building blocks provide opportunities to tailor the design of BsAbs and TsAbs to match the desired applications.