The idea of using the specificity of antibodies to target malignant cells was put forward very soon after the discovery of techniques to generate monoclonal reagents. The responses seen with mouse anti-idiotype in patients with B-cell lymphomas indicated the potential of this approach, but it was some years before key technical obstacles were overcome and the more widespread application of these therapies became possible. Whilst they were originally conceived as having an immunotherapeutic effect, it has become clear that recruitment of immune effectors is only one component of successful antibody therapy, and their action upon the cellular target, either blocking or agonistic, is also critical. The development of immunoconjugates to deliver toxins or radiation is a further extension of the approach, and here again the intracellular effect of antibody ligation appears to be crucial. This presentation will address the central theme of antibody treatments for malignancy that are now reaching the clinic, and will use these examples to highlight ways in which antibodies may be acting in vivo.