In the past 20 years researchers have attempted to activate the host immune defence system to kill tumour cells and eradicate cancer. In some cases, the response of patients to immunotherapy has been extremely successful; however, other trials have shown disappointing results, and so there is a clear need for more effective therapies that can effectively adjunct conventional approaches. Interleukin 21 (IL21) is a new immune-stimulating cytokine that has demonstrated antitumour activity in several preclinical models, and has recently undergone Phase I trials in metastatic melanoma and renal cell carcinoma. Here, we provide an overview of the antitumour effects of IL21 and describe strategies to combine IL21 with other drugs for future cancer therapies.