It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents--including classical chemotherapeutics and targeted compounds--stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications.