Cardiovascular disease is a leading cause of death worldwide and accounts for greater than 17.3 million deaths per year, with an estimated increase in incidence to 23.6 million by 2030 1. Cardiovascular death represents 31% of all global deaths 2 - with stroke, heart attack, and ruptured aneurysms predominantly contributing to these high mortality rates. A key risk factor for cardiovascular disease is hypertension. Although treatment or reduction in hypertension can prevent the onset of cardiovascular events, existing therapies are only partially effective. A key pathological hallmark of hypertension is increased peripheral vascular resistance due to structural and functional changes in large (conductive) and small (resistance) arteries. In this review, we discuss the clinical implications of vascular remodeling, compare the differences between vascular smooth muscle cell (VSMC) remodeling in conductive and resistance arteries, discuss the genetic factors associated with VSMC function in hypertensive patients, and provide a prospective assessment of current and future research and pharmacological targets for the treatment of hypertension.