Hypertension is an important public health challenge because of its high prevalence and strong association with cardiovascular disease and premature death. Hypertension is a major cause of CKD, is present in more than 80% of CKD patients, and contributes to CKD progression. Risk factors for hypertension include, but are not limited to, age, race, family history, obesity, physical inactivity, tobacco use, and inadequate intake of minerals such as calcium, potassium, and magnesium. Magnesium is the second most abundant intracellular cation in the human body and plays an important role in insulin and adenosine triphosphate metabolism. Low dietary magnesium intake has been associated with an increased risk of developing hypertension in prospective cohort studies. Moreover, clinical trials suggest that magnesium supplementation has blood pressure-lowering effects. In addition, emerging data reveal potential mechanisms by which magnesium may influence blood pressure. Here, we will review these mechanisms, using a physiology-based approach, focusing on the effects of magnesium on total peripheral resistance and cardiac output.