This chapter focuses on gene transfer, which has played a significant role in understanding the biological activity of cytokines, the role of cytokines in disease, and for the development of clinical approaches for treating a wide variety of diseases. Gene transfer of cytokines to cells in culture or in vivo can be accomplished by a variety of gene transfer vectors, including both viral- and non-viral-based vectors. For specific gene transfer applications, certain vectors have their own advantages and disadvantages. The majority of phase I clinical trials using cytokine gene transfer have not shown significant efficacy. However, it is likely that if the biology of cytokines is known, especially on how multiple cytokines work synergistically to regulate the immune response, then the cytokine gene therapy will play a significant role in the treatment of many human diseases.