Clinicians and scientists have long questioned whether the immune system has a role in destroying cancerous tissue. Studies performed in animal models have, however, recently revealed that the immune system can, at least in principle, effectively control tumours. In parallel with these findings, a large body of evidence indicates that although the immune system has the capacity to control tumours, there are also regulatory mechanisms that subdue these responses. A major challenge of tumour immunotherapy, therefore, is to find ways of disabling these regulatory functions while restoring or priming any immune responses that are protective.