Multimodal analgesia refers to the practice of combining multiple analgesic drug classes or techniques to target different points along the pain pathway in an effort to improve analgesia. This strategy requires an understanding of pain physiology and pathophysiology so pharmacologic interventions can be tailored to meet the needs of the patient. This article reviews the physiologic basis of pain as it relates to analgesic treatments and also introduces new developments in molecular biology that may guide analgesic drug development in the future.