Recent studies indicate that cytokines produced by cells of the innate defense system play an essential role in influencing the immune response towards protective antitumor immunity. These cytokines might act as first ‘danger signals' in alerting the immune system. By promoting the differentiation and activation of dendritic cells, antigen presentation and T-cell-mediated immune responses, these cytokines could be powerful natural adjuvants for the development of cancer vaccines. With regard to type I interferons – cytokines with a long history of clinical use – this new knowledge could be translated easily into novel strategies for the prevention and treatment of human malignancies.