<p>Hypertension, or persistently elevated blood pressure, affects about one third of the adult population worldwide and causes approximately 8.5 million deaths annually. Family studies have demonstrated that blood pressure shows substantial heritability, suggesting that genetic factors contribute to hypertension. Linkage studies and next-generation sequencing efforts have identified several variants with large effect sizes that cause rare monogenic hypertension syndromes. These syndromes often present with early onset and typically affect adrenal and renal regulation of salt reabsorption. In addition, somatic (tumour-specific) mutations have been identified in hormone-producing tumours that cause hypertension (phaeochromocytomas, aldosterone-producing adenomas, cortisol-producing adenomas, pituitary adenomas, reninomas). However, most cases of hypertension are polygenic. Large genome-wide association studies have identified many variants with small effect sizes that add to our understanding of blood pressure as a complex trait. Epigenetic mechanisms also influence gene expression and contribute to blood-pressure alterations. Several proteins that are affected by Mendelian diseases are targets of existing antihypertensive drugs and other such proteins may be good candidates for future drug development.</p>