Essential hypertension (EH) is thought to be a multifactorial disease. In Japan, there are more than 20 million cases of EH, which accounts for 80 to 90% of hypertension cases in Japan. It is very difficult to isolate the susceptibility genes of EH in familial linkage analysis such as sib-pair analysis and association studies such as case-control studies of candidate genes. Whole genome scanning and haplotype analysis using genetic markers will be widely conducted in the future. The present paper contains a review of issues and progress in isolation of susceptibility genes of EH, and an introduction to an effective novel method for isolation of susceptibility genes of EH.