The processes controlled by cytokines may be co-opted by pathologic states, contributing to processes that threaten host well-being. A nuanced understanding of this immense web of chemical communications will allow us to understand the mechanisms and limitations of current therapies and to enhance their therapeutic benefits while minimizing their toxicities. This article reviews the current state of cytokine science in malignancy, focusing on agents that are approved for therapy or are in late-stage development. Promising new directions, including novel engineered.