© 2014 by Nova Science Publishers, Inc. All rights reserved. Interleukin-2 (IL-2) is an important T cell growth factor with the capacity to promote T cell expansion. Consistent with this idea, IL-2 is used clinically to enhance T cell responses to viral and tumor antigens in both preclinical models and patients. However, the role of IL-2 in immune responses is far more complex than initially expected. In addition to its ability to promote immune responses, IL-2 signaling is essential for the differentiation of regulatory T cells (Tregs), which suppress immune responses. Thus, IL- 2 signaling can both promote and inhibit immune responses depending on the context, the dose, and the nature of the IL-2/IL-2 receptor interactions. As a result, IL-2 therapies that selectively target Tregs may be useful for treating autoimmune diseases, whereas IL-2 therapies that selectively target effector T cells may improve cancer immunotherapy. In this chapter we summarize our current understanding of the biology of IL-2-based immunotherapies for cancer and autoimmune disease.