Molecular pain research is a relatively new and rapidly expanding field that represents advancement in conventional pain research. One of the fundamentals of molecular pain involves the cloning of genes and especially the ion channels specifically involved in nociceptive processing at the periphery and centrally. A variety of approaches were used to isolate these critically important genes. Cloning of these genes involved innovative strategies based on existing molecular approaches. This review will discuss well-utilized cloning approaches and their exploitation in molecular pain research.