Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant clinical heterogeneity. Its pathogenesis is complex and involves multigenic components, dysregulation of T and B lymphocytes and the presence of autoantibodies, which form the basis for inflammation, and the pathology found in the various organ systems. Traditional treatments for SLE have included non-steroidal anti-inflammatory drugs, antimalarials, corticosteroids, and cytotoxic/immunosuppressants, but a recent emphasis on the development of biological agents that inhibit autoreactive B cells, interrupt cytokine signaling and facilitate the development of regulatory T cells has become a new modality in treating the disease. This review will delve into the pathogenesis of the disease process, as well as the current and up and coming novel biological treatment and other therapies for specific disease manifestations, such as neuropsychiatric SLE and cutaneous lupus erythematosus, and detail the shift to immune targeted therapies and novel treatments being developed for specific manifestations of the disease.