Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by pathologic manifestations in multiple organs and elevated morbidity. Traditional management of SLE has included the use of nonsteroidal anti-inflammatory drugs, anti-malarials and immunosuppressive drugs such glucocorticoids, azathioprine, cyclophosphamide, and mycophenolate mofetil. Although many of these therapies have shown great efficacy, they often associate with adverse effects, due to their systemic activity. The development of safer therapies for SLE has led to recent emphasis on targeting selected pathways that can be important in the inflammatory response in SLE. In this context, the use of biological agents such as monoclonal antibodies has seen a rapidly increasing progress, and is poised to be some part of the clinical practice for SLE in a near future. This review provides an update on the ongoing clinical trials and the promise and obstacles in the use of biologics in SLE.