Despite the many advances in our understanding of the mechanisms underlying pain processing, pain continues to be a major healthcare problem in the United States. Each day, millions of Americans are affected by both acute and chronic pain conditions, costing in excess of $100 billion for treatment-related costs and lost work productivity. Thus, it is imperative that better treatment strategies be developed. One step toward improving pain management is through increased knowledge of pain physiology. Within the nervous system, there are several pathways that transmit information about pain from the periphery to the brain. There is also a network of pathways that carry modulatory signals from the brain and brainstem that alter the incoming flow of pain information. This article provides a review to the physiology and processing of pain.