Despite significant advances in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), there are only a few drugs approved by the regulatory agencies across the world for the treatment of these patients; in fact, many of the compounds subjected to clinical trials have failed in achieving their primary endpoints. Current therapeutic options include antimalarials which should be used in all SLE patients unless they are strongly contraindicated, glucocorticoids which should be used at the lowest possible dose and for the shortest possible time, and immunosuppressive drugs which should be used judiciously, mainly in patients with severe organ involvements or receiving high doses of steroids to control their disease. Despite improvement on the survival of SLE patients, damage accrual has not varied over the last few decades, reflecting a gap between these therapeutic options and the expectations of these patients and their treating physicians. Biologic compounds can be used in some refractory cases. However, their cost is of great concern for both the patients and the health system. Cost is of special importance in low-income countries, because low-income SLE patients tend to experience a more severe disease having an overall worse prognosis which is compounded by their limited access to the health system. Although a treatment to target based on defined molecular pathways for specific disease subsets is appealing, this is not yet a reality. This review addressed current therapeutic options for SLE patients and the state of the art of investigational drugs targeting pathogenic pathways identified in these patients.