Hypertension is a complex quantitative trait under polygenic control. The identification of genes responsible for high blood pressure is of major importance, because it provides a mechanistic classification of the common phenotype and guide therapy tailored to the underlying primary abnormality. Experimental studies have identified several quantitative trait loci for blood pressure and other cardiovascular phenotypes. Further strategies that include congenic and subcongenic lines should ultimately lead to positional cloning of the causative genes, but this final step remains elusive at present. Human studies have focused on the rare Mendelian forms of human hypertension or candidate gene studies. Moreover, two recent examples show direct translation of a candidate gene and a quantitative trait locus from the experimental setting to human investigation. These strategies, together with new molecular genetic tools, will ultimately result in the identification of major genes contributing to human essential hypertension.