Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several clinical and immunological manifestations, lacking accurate methods of diagnosis and treatment. This article focuses on the latest research in SLE’s epidemiology, diagnosis methods, and treatment strategies. SLE has a gender-based and ethnicity- based prevalence, with more cases observed in females than males and African population than Caucasians. The diagnosis of SLE is also challenging due to the multifactorial nature of the disease. The diagnosis is generally based on classification rather than diagnostic criteria. Several classification criteria have been proposed, with the most important being ACR-1997, SLICC-2012, and EULAR/ACR-2019. The latest criteria suggested the use of weights linked to different clinical and immunological manifestations. Moreover, several treatment therapies have also been proposed to treat SLE. Anti-malarial drugs are generally regarded as suitable in the earlier stages of SLE. The standard therapy against SLE is mycophenolate mofetil, except for ongoing pregnancy, where azathioprine is used. Currently, different immunosuppressants and immunomodulators are being evaluated in clinical studies against SLE. Anyways, a combination of different therapies might be a holistic approach to the disease, but the heterogenicity of SLE still remains a challenge.