Since the joint is the target organ of non steroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases, the concentration in the synovial fluid (SF) is an important determinant of clinical response to these agents. Present data indicate that in the SF pharmacokinetic behaviour of NSAIDs depends on their plasma elimination half-life. Moreover, some chiral drugs exhibit stereoselective distribution properties. Finally, pharmacodynamic investigations suggest that inhibition of prostaglandin synthesis in the synovial compartment is the dominant mechanism of action for most, if not all, NSAIDs.