Ischemic stroke is a major cause of death and disability in adult Chinese people. Proinflammatory cytokines may exacerbate ischemic brain injury after stroke. However, preclinical studies have shown that targeted inhibition of interleukin (IL)-1β, IL-6, and/or tumor necrosis factor-α (TNF-α) alleviated ischemic brain injury. But the efficacy of these strategies has not yet been confirmed in clinical trials. Further studies are needed to investigate the effect of anti-inflammatory therapy for stroke in clinical settings. Therefore, this article focuses on classical proinflammatory cytokines including IL-1β, IL-6, and TNF-α, and summarizes their roles and mechanisms in ischemic brain injury and progress in clinical translational research.