Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by the overproduction of organ-specific autoantibodies to various components of the cell nucleus and by the development of immune-mediated inflammatory damage to internal organs. SLE is the prototype of a systemic human autoimmune disease; it is an extremely heterogeneous disease in terms of both clinical manifestations and a genetic predisposition and pathogenetic mechanisms, which often complicates the early diagnosis of the diseases and makes it impossible to personify therapy. Despite the fact that in the 21st century, the 15-year survival rate for SLE has increased up to 85%, the inadequate control of disease activity and the need for almost constant intake of glucocorticoids and immunosuppressive drugs result in the accrual of irreversible damages to internal organs and, as a consequence, in decreases in quality of life, disability, social maladaptation, and premature death. The paper considers the new 2019 EULAR/ACR diagnostic criteria for SLE, the contemporary 2019 EULAR recommendations for the management of SLE, and new pharmacotherapy options for this condition, which are based on the deciphering of the mechanisms of SLE immunopathogenesis.