Systemic lupus erythematosus (SLE) is a highly heterogeneous disease affecting multiple organs and is characterized by an aberrant immune response. Although the mortality of SLE has decreased significantly since the application of glucocorticoids, severe or refractory SLE can potentially cause irreversible organ damage and contribute to the disease morbidity and mortality. Early recognition of severe SLE or life-threatening conditions is of great challenge to clinicians since the onset symptoms can be rapid and aggressive, involving the visceral organs of the neuropsychiatric, gastrointestinal, hematologic, renal, pulmonary, and cardiovascular systems, etc. Additionally, SLE patients with specific comorbidities and detrimental complications could lead to a clinical dilemma and contribute to poor prognosis. Prompt and adequate treatment for severe refractory SLE is crucial for a better prognosis. However, as evidence from well-designed randomized controlled trials is limited, this review aims to provide real-world evidence based on cohort studies from Peking Union Medical College Hospital, the national tertiary referral center in China, together with the literature, on clinical characteristics, risks and prognostic factors, and treatment strategies for severe and/or refractory SLE.