This chapter explores that the study of inflammation and anti-inflammatory drugs gained considerable impetus from the demonstration in 1949 of the antirheumatic action of cortisone. Despite a considerable amount of research and an even greater amount of speculation, the mechanism of action of anti-inflammatory compounds is still largely unknown. Indeed, the new anti-inflammatory drugs that have appeared during the past few years have been developed based on empirical screening procedures. A fundamental difference in the mode of action separates the glucocorticoids, such as cortisone, from chemically heterogeneous groups of compounds, including the salicylates and pyrazolones, which exhibit some similarities in their anti-inflammatory effects. The chapter describes inflammation as a series of localized tissue responses to foreign stimuli, which may be biological, chemical, or physical. Apart from external stimuli, it now appears than an endogenous factor, the autoimmune reaction, may initiate an inflammatory response. Although it is now universally accepted that inflammation serves the useful purpose of minimizing the damaging effect of the causative irritant, there are circumstances when both acute and chronic inflammation appear to be wholly detrimental to the host as, for example, in rheumatic and allergic diseases. It is the clinical problem posed by these diseases that has stimulated most of the research into the development of anti-inflammatory drugs.