Intake of salt is a biological imperative, inextricably woven into physiological systems, human societies and global culture. However, excessive salt intake is associated with high blood pressure. As this effect likely drives cardiovascular morbidity and mortality, excessive salt intake is estimated to cause ~5 million deaths per annum worldwide. Animal research has identified various mechanisms by which high salt intake drives disease in the kidney, brain, vasculature and immune system. The potential for therapeutic interventions in many of these pathways has yet to be tested. Salt-reduction interventions lower blood pressure, but for most individuals, ‘hidden’ salt in processed foods disconnects salt intake from discretionary control. This problem is compounded by growing inequalities in food systems, which form another hurdle to sustaining individual dietary control of salt intake. The most effective salt-reduction interventions have been implemented at the population level and comprise multi-component approaches, involving government, education and the food industry.