Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. The treatment target of SLE should be remission of systemic symptoms and organ manifestations or attainment of the lowest possible disease activity, measured by at least one validated disease activity index and/or by organ-specific markers. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Moreover, each patient may manifest different symptoms and variable disease activity and severity, as well as therapy-related adverse effects. SLE patients frequently have numerous comorbidities, such as hyperlipidemia and hypertension, which represent risk factors for accelerated atherosclerosis and cardiovascular disease and depression, which can seriously compromise health-related quality of life. This chapter focuses on conventional management of SLE patients, including nonpharmacologic measures and pharmacological therapies.