This article reviews the innervation of the arterial system of the lower extremity, lumbar sympathectomy in vascular surgery, lumbar sympathectomy for digital gangrene and in the prevention of major amputation of the lower extremity and substance P's role in neurogenic inflammatory modulation. Long-term results of lumbar sympathectomy and direct arterial bypass surgery have also been reviewed. In addition to the pilomotor, sudomotor and vasomotor actions of the sympathetic nervous system via its neurotransmitters, the molecular basis of the chronic neurogenic inflammatory reaction have been addressed with special attention to the discovery of substance P in the lumbar sympathetic chain and ganglia of human beings.