Abstract: Belimumab is a human monoclonal antibody that inhibits B-cell activating factor of the tumor necrosis factor family(BAFF). With the approval of belimumab for treating patients with systemic lupus erythematosus (SLE), targeted biologics has generally ushered a new era in the treatment of SLE. The pathogenesis of SLE involves a general breakdown in both B cell and T cell tolerance. In this review, we focused on the new promising therapeutic targets and several ongoing clinical trials for SLE. The approaches of these biologic therapeutic agents included targeting B cell selective cell surface molecules (CD20 or CD19), inhibiting B cell survival by targeting cytokines and signaling molecules (BAFF or a proliferation-inducing ligand), interfering with B cell antigen presentation by targeting co-stimulatory molecules (CD40-CD40 ligand interactions or ICOS-ICOS ligand interactions), blocking the signal pathways (rigerimod, interferon-α, or JAK/STAT), et al. Biologic target therapies for SLE have made some progress and bringing successful new biologic therapies into the clinical practice for SLE remains challenging but promising in the future.