Interleukin 21 (IL-21) is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer (NK) cells and cytotoxic T cells that can destroy virally infected or cancerous cells. IL-21 is noted to have anti-tumour effects through continued and increased CD8+ cell response to achieve enduring tumor immunity. IL-21 may contribute to the mechanism by which CD4+ T helper cells orchestrate the immune system response to viral infections. In HIV infected subjects, IL-21 has been reported to critically improve the HIV-specific cytotoxic T cell responses and NK cell functions. IL-21 was approved for Phase 1 clinical trials in metastatic melanoma (MM) and renal cell carcinoma (RCC) patients. IL-21 proceeded to Phase 2 clinical trials where it was administered alone or coupled with drugs as sorafinib and rituximab.