The inflammatory response involves a complex set of stereotyped biochemical and cellular reactions that aim to eliminate pathogens. Systemic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, feature a persistent, uncontrolled inflammatory response that typically culminates in tissue damage. The control of this inflammatory response is of paramount importance in preventing irreversible tissue damage, as well as in controlling symptoms. NSAIDs and corticosteroids are the most effective agents currently available to control the clinical manifestations of inflammation, although they usually need to be used in conjunction with other "disease modifying" strategies in order to achieve optimum control of chronic inflammatory disorders. As with all pharmacologic therapy, the risk to benefit ratio of each agent needs to be considered carefully before embarking on extended courses of therapy. Strategies to minimize the long-term risks of NSAIDs and corticosteroids are continuing to evolve and hold the promise of greater safety without loss of efficacy.