Systemic lupus erythematosus is a multiorgan autoimmune disease with a highly variable clinical course, typically involving women in childbearing age. At present, many aspects of its pathogenesis still remain unclear. Moreover, although a significant increase of patient survival has been observed in the last decades, morbidity and mortality remain high. Finally, SLE impacts negatively on the health-related quality-of-life of patients. Therefore, multiple aspects of SLE still remain challenging and it continues to be the object of both clinical and translational clinical research. Herewith, we provide a critical digest of the recent literature on this topic.