About three decades ago, the primary mechanism of action of the non-steroidal anti-inflammatory drugs (NSAIDs) was elucidated when their inhibitory action on the production of prostaglandins was discovered. It was found that their action is centred on the inhibition of the cyclooxygenase (COX) enzyme responsible for converting arachidonic acid to prostaglandins. More recently, it was discovered that at least two isoforms of the enzyme exist. While the COX-1 isoenzyme is mainly constitutive, the COX-2 form is inducible. The constitutive form is principally associated with physiological/homeostatic functions while the inducible form is involved in inflammatory responses. Because many of the unwanted effects of the NSAIDs have been associated with COX-1 inhibition, specific drugs with a high inhibitory activity toward the COX-2 isoenzyme have been developed in recent years. The efficacy, safety and potential clinical roles of these COX-2-specific inhibitors are addressed in this review article.