Bispecific antibodies (BsAb) can, by virtue of combining two binding specificities, improve the selectivity and efficacy of antibody-based treatment of human disease. Recent studies underline the importance of both the 'anti-trigger' and 'anti-target' modalities of BsAb for therapeutic efficacy. Several BsAb induce effective cytotoxicity as well as 'vaccine effects' in vivo. Here, Annemiek van Spriel and colleagues discuss how these results have catalysed renewed efforts to translate BsAb concepts into effective therapies.