The classical heterocoupling of a 1-haloalkyne with a terminal alkyne catalyzed by copper salts in the presence of a base for the synthesis of unsymmetrical diynes is termed the Cadiot–Chodkiewicz coupling reaction. The diynes are of great importance due to their biological, optical and electronic properties. A number of modifications have been developed recently to improve the efficiency of Cadiot–Chodkiewicz coupling reactions in terms of selectivity and yield. This is the first review on the Cadiot–Chodkiewicz cross-coupling reaction which highlights the modern approaches and protocols developed for the synthesis and applications of unsymmetrical 1,3-diynes.