A definite epidemiological association exists between kidney stone disease and arterial hypertension, but the pathophysiological mechanisms are still not fully understood. Hypercalciuria or inflammation and oxidative stress have been proposed as possible links. However, there is more convincing evidence that the association between nephrolithiasis and hypertension may be considered as a part of the association between kidney stone disease, metabolic syndrome and atherosclerosis. From a clinical point of view, this association represents a crucial aspect of the clinical management of patients affected by kidney stone disease. In order to implement early prevention and treatment of cardiovascular and/or renal damage physicians should be encouraged to assess individual cardiovascular risk factors in any adult with kidney stones. Consequently, patients with kidney stones need a comprehensive approach rather than an intervention limited to the urinary tract and focused on stone resolution and recurrence prevention. It is time to view kidney stone disease as a systemic disorder, associated to or predictive of hypertension, chronic kidney disease, bone and cardiovascular damage. All these conditions negatively affect patient prognosis. This multi-systemic approach could increase the clinical impact of the kidney stone clinic.