<p>Cytokines are a class of secreted proteins that transmit critical signals between cells to maintain homeostatic balance, coordinating processes such as proliferation, migration, polarization, and survival. Cytokines play a particularly important role in regulating the immune system through activation of either proinflammatory or anti-inflammatory pathways on a variety of hematopoietic and nonhematopoietic cell types. As a consequence of their essential roles in dictating cell fate, especially in the context of immune responses, cytokines have become an appealing target for the development of drugs to treat immune-linked diseases. With respect to oncology applications, therapeutic efforts have primarily focused on either promoting the effects of immunostimulatory cytokines or antagonizing the effects of immunosuppressive cytokines, with the goal of stimulating antitumor immunity. Here, we provide an updated overview of preclinical and clinical therapeutic advances in the design of cytokine antagonist antibodies for cancer treatment. We first discuss the structural and functional characteristics of various cytokines, including interleukins, chemokines, and growth factors, as well as their contributions to cancer development and progression. We then highlight successes and failures in generating therapeutic antibodies against each of these cytokines. As the functions of cytokines are complex and multifaceted, we note that complete ablation of cytokine activity may not be therapeutically desirable and that combination strategies are often needed to realize the full potential of anti-cytokine antibodies as therapies. Looking ahead, innovative approaches and novel antagonistic scaffolds promise to continue advancing clinical progress for this important category of oncology drugs.</p>