Survival of patients with systemic lupus erythematosus (SLE) has greatly improved over the decades. Many reasons for treatment withdrawal may be faced by the physician during the disease course, such as inactivity of disease, damage accrual, risks of long-term side effects, or potential interactions with other drugs required to treat concomitant conditions, as well as patients' preferences. Therefore, analysis of long-term therapy and treatment withdrawal is important. We have examined the available literature concerning withdrawal of therapy, with attention to glucocorticoids, antimalarial drugs and traditional immunosuppressive drugs in SLE patients who did not have renal disease. We expanded our search to address two questions: i) advantages of long-term therapy in SLE (i.e. reduction of flares, reduction of damage accrual, improved survival); and (ii) burden/side effects of therapy in SLE. Studies are needed to: i) define remission in SLE; ii) define the advantages of long-term therapy in non-renal lupus in terms of prevention of flares; iii) clarify the risks related with long-term immunosuppressive therapy; iv) identify the appropriate patient at the appropriate time for withdrawal of corticosteroids or immunosuppressive therapy; and v) define withdrawal/tapering strategies.