All nonsteroidal anti inflammatory drugs (NSAIDs) are characterized by a high degree of protein binding and small volumes of distribution. Differences in clearance account for the variability in half-life among these drugs. The majority are metabolized by the liver through a variety of pathways. These drugs are subject to drug interactions of several mechanisms, including protein-binding-displacement interactions, induction or inhibition of hepatic drug metabolism, and competition for active renal tubular secretion with other organic acids. NSAIDs are also subject to special pharmacokinetic considerations about which a great deal has been learned recently. These include data demonstrating that assessment of disposition of these drugs using only total drug concentrations can be misleading and that one must instead assess the disposition of unbound, pharmacologically active drug. Second, it appears that only one enantiomer of the propionic acid NSAIDs is active; studies of the pharmacokinetics of this class of NSAID should include assessment of the active stereoisomer. Finally, the propionic acid NSAIDs are metabolized to acyl-glucuronide conjugates, which are unstable and can cleave back to the parent drug. This feature allows the paradox of a drug that is metabolized by the liver being able to accumulate in patients who have renal insufficiency. Because of these newer pharmacokinetic considerations, much of the old data concerning the clinical pharmacology of NSAIDs are obsolete. More precise new information is needed in this area.