In recent years, there has been an ever‐increasing need for rapid reactions that meet the three main criteria of an ideal synthesis: efficiency, versatility, and selectivity. Such reactions would allow medicinal chemistry to keep pace with the multitude of information derived from modern biological screening techniques. The present review describes one of these reactions, the 1,3‐dipolar cycloaddition (“click‐reaction”) between azides and alkynes catalyzed by copper (I) salts. The simplicity of this reaction and the ease of purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The present review will outline the accomplishments of this strategy achieved so far and outline some of medicinal chemistry applications in which click‐chemistry might be relevant in the future. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 278–308, 2008