Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most frequently prescribed medicine in the world. Their main disadvantages were related to their effect on the gut and kidney. Since the early 80s of the last century, drugs manufacturers try to discover a NSAIDs which does not affect the gut and kidney .The gut toxicity may be decrease by concomitant use of antisecretery agents, but this increase their cost and decrease the compliance. The fully selective cyclooxygenase inhibitors has been introduced recently as an alternative to old generation NSAIDs.Unfortunaltly subsequent long-term evaluation produced disappointing results, and opened the door for a lot of discussion and controversies.