Arterial sympathetic innervation (ASI) is a complex biological process requiring a fine axonal guidance by arteries. Its physiological impact has remained unknown for decades but recently started to be better understood and recognized. ASI is a key element of the adaptive response of the cardiovascular system to challenging situations (exposure to cold, exercise…) as ASI controls the diameter of resistance arteries, thus blood supply to organs and systemic arterial blood pressure via arterial tone modulation. Defaults in ASI can lead to diseases, acting as a main cause or as an aggravating factor. Its impact is actively studied in cardiovascular diseases representing major public health issues, like hypertension, but ASI could also play a role in aging and many more pathological processes including cancer.