The aim of cancer immunotherapy is to employ the specificity of the immune system to provide a more effective, less toxic, treatment compared with conventional therapies. Although many strategies have been used to try to generate effective anticancer immune responses, very few have reached mainstream clinical use. A new approach introduced over the last few years is to use immunostimulatory mAbs (monoclonal antibodies) to boost weak endogenous antitumour immune responses to levels which are therapeutic. Such agonistic or antagonistic mAbs bind to key receptors in the immune system acting to enhance antigen presentation, provide co-stimulation or to counteract immunoregulation. In animal models, this approach has been shown to promote powerful tumour-specific T-cell responses capable of clearing established tumour and leaving the animal with long-term immunity. In addition to this impressive therapy seen in tumour models, these same mAbs also have the potential to be therapeutically useful in autoimmune and infectious diseases. This review discusses the use of these mAbs as therapeutic agents, their advantages and disadvantages and the challenges that need to be overcome to use them clinically.