Systemic lupus erythematosus (SLE) is a chronic autoinflammatory disease of unknown etiology with predominance of the female sex. Clinical criteria as well as immunological characteristics, e. g. autoantibodies, are necessary for diagnosis. The clinical course of SLE is variable and may be characterized by periods of remissions and chronic or acute relapses. New symptoms are often challenging regarding differential diagnosis. This review will discuss symptoms with a problem based approach. Parameters of activity are helpful to differentiate between disease activity and associated problems, e. g. infections. Lupus patients have a 5 times increased mortality compared to the normal population. The main reasons for mortality are infections and cardiovascular events, rather than disease manifestations. Therefore, besides the fast and precise use of immunosuppressants the consequent therapy of co-morbidities is a major issue in dealing with these patients. Cardiovascular risk factors need to be controlled, life style modifications should be started early, and diagnosis and therapy of osteoporosis should not be neglected.