Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its variable course makes it difficult to standardize patient treatment. This article aims at a literature review on available drugs for treating SLE and on drugs that have shown therapeutic effects in this disease. The PubMed/MEDLINE electronic search engine was used to identify relevant studies. This review presents the current therapeutic options, new biological therapies, and combination therapies of biologics with standard immunosuppressive and immunomodulating drugs. We have also underlined the importance to implement the treat-to-target strategy aimed at reducing or discontinuing therapy with glucocorticosteroids (GCs). The awareness of the benefits and risks of using GCs helps in refining their dosage and thereby obtaining a better safety profile. The advent of biological targeted therapies, and more recently, low-molecular-weight compounds such as kinase inhibitors, initiated numerous clinical trials in SLE patients and led to the approval of two biological drugs, belimumab, and anifrolumab, for SLE treatment. Progress in the treatment of SLE was reflected in the 2019 and 2021 recommendations of the European Alliance of Associations for Rheumatology (EULAR). However, a mass of recent clinical research data requires continuous consolidation to optimize patient outcomes.