The term cytokine describes a group of protein cell regulators involved in the control of cell growth and differentiation in embryogenesis, immunity and inflammation. They are of low molecular weight, are produced locally, and act in an autocrine or paracrine manner. In the past decade their use as cancer therapy has become a reality. Thirty years ago mice were treated with the antiviral protein interferon (IFN) which not only produced a reduction in the incidence of virus-induced tumors but also slowed the development of transplantable tumors. This was one of the first indications that cytokines can be negative regulators of cell growth. Here we outline current knowledge of the actions of IFNs and other cytokines in animal models, and draw parallels with clinical trials to illustrate the invaluable nature of this preclinical and mechanistic work.