The genetics of essential hypertension has proven refractory to molecular and epidemiological genetic approaches despite the early successes in identifying the genes involved in rare monogenic forms of hypertension. The problems facing the genetic studies for hypertension are not unique, but phenotypic characterization, heterogeneity and high prevalence make it a special case requiring a more individualized approach. We describe the current status of hypertension and blood pressure gene mapping strategies and summarise the key evidence for rare and common variants in the causation of hypertension. We explore intermediate phenotypes and pharmacogenetics as efficient strategies which have the potential to produce clinically translatable discoveries. The global health impact of hypertension is considerable and by understanding the genetic factors elevating blood pressure it may be possible to develop enhanced strategies for diagnosis, prevention or treatment.