CD40 is a tumour necrosis factor receptor family member that is overexpressed in a broad range of leukaemias, lymphomas and carcinomas, and could contribute to their development. Recent experimental and clinical observations suggest that the CD40 pathway can be exploited for the treatment of malignancy. The mechanisms by which CD40 activation exerts anti-tumour effects include inhibition of tumour cell proliferation, sensitisation to other anti-cancer agents, including cytotoxic drugs, upregulation of immune processing and presentation within the malignant cells, and stimulation of anti-tumour immune responses via activation of dendritic cells. Thus, the CD40 pathway provides an opportunity to muster different anti-cancer approaches in one therapy, and offers an attractive option for future clinical trials.