To successfully manage pain clinically, it is essential to begin with an understanding of the underlying mechanisms responsible for its generation. A skillful approach based on better knowledge concerning anatomical structures, pathways, and events that result in pain is more likely to lead to effective clinical management of pain. This discussion will include an overview of the entire pain pathway explained in simple terms to help foster improved outcomes through patient education and to offer insight as to the pharmacologic and nonpharmacological targets considered when treating pain.