I discuss the identification and cloning of genes involved in determining susceptibility to diseases under polygenic control. The process of cloning a susceptibility gene is as follows: identification of new genetic markers in the region by database analysis, isolation of DNA clones in the region and the generation of new genetic markers, refinement of the map position using these markers for linkage disequilibrium analysis, construction of a physical and disequilibrium map, construction of a clone contig across the critical region in yeast artificial chromosomes, PAC, bacterial artificial chromosomes and cosmids, and finally gene identification and etiological mutation detection.