Background: The systemic lupus erythematosus (SLE) is a chronic prototypical systemic autoimmune disease with extremely varied clinical manifestations, pathogenesis, and epidemiological burden worldwide among different racial, ethnic age, and gender groups. The disease has a complex form of pathogenesis that is not fully understood as SLE has extremely varied clinical manifestations and continues to have unpredictable courses. However, the approach to SLE imposes complex modalities of management and highly experienced clinicians. Initial clinical evaluation and new classification criteria are anticipated for a better diagnostic approach. Objective: To assist internists in understanding Systemic Lupus erythematosus and the constantly evolving diagnostic criteria and recommended modalities of management, as well as observing the major risk factors. Methodology: This review included clinical evidence-based guidelines conducted and analyzed by the PubMed search and only English articles, documents, and evidence-based clinical trials were included. The terms were applied within the title or abstract title ((“SLE "[Mesh] AND “Lupus” Mesh] AND “Criteria"[Mesh]AND “Management"[Mesh]). Conclusion: The new criteria structure will prove useful in the diagnosis of questionable SLE patients. Approach to SLE involves complex modalities of treatment and early detection of SLE comorbidities is the cornerstone of management.