Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can form immune complexes and deposit in tissues, causing inflammation and organ damage. There is evidence that interferons and some interleukins can have an active role in the pathogenesis of SLE and can contribute significantly to the immune imbalance in the disease, whereas the role of some cytokines (such as TNF) is still debated. This review discusses the activity of several cytokines in SLE, their effects on the immune cells in relation to the disease pathogenesis, and the promise and limitations of cytokine- based therapies in clinical trials for lupus patients.