Cytokines regulate and control the immune system. In systemic lupus erythematosus, several of these cytokines are overexpressed and contribute to the pathogenesis of the disease. Cytokine inhibition has been successfully used to treat other rheumatic and autoimmune diseases, and several cytokines are currently being investigated to determine whether inhibition would be therapeutic in lupus. The cytokines discussed in this review have all undergone clinical trials, and include TNF-α, IL-1, IL-6, IL-10, IL-15, IL-17, IL-18 and IL-23. Inhibition of the majority of these targets was safe and showed some efficacy in treating lupus. Cytokine inhibition strategies have just started to realize their potential for the treatment of this difficult disease, and show great promise for the future.