Sodium consumption is a target for prevention of cardiovascular disease (CVD). The relationship between sodium intake and blood pressure (BP) is well-established, but the relationship with CVD is less clear. This review focuses on studies investigating the association between sodium intake and CVD within five principal subgroups: age, underlying BP, gender, body size, and ethnicity. We conclude that sodium reduction results in decreased CVD risk in the general population, and some susceptible subgroups may especially benefit from preventive efforts. Older individuals, those with underlying elevated BP, and those with increased body size may benefit most, but men and women of all ages, ethnicities, and normotensives also experience reduced CVD risk in relation to lowered sodium intake. Public health policy to reduce sodium intake in the United States would have significant cost-savings, far greater than the cost of intervention, and would also result in a significant gain in quality-adjusted life years.