Multimodal analgesia (MMA) is the simultaneous use of multiple analgesic medications that work in a synergistic manner to provide pain control. In recent years, spine surgery has seen the growth of multimodal perioperative protocols for managing pain. Postoperative pain following spinal procedures is a common complaint, with persistent pain even after the immediate convalescent period leading to negative impacts on health. A multidisciplinary approach is essential in reducing postoperative morbidity and complication rates. This review demonstrates the efficacy in the combined use of opioid-alternative medications such as NSAIDs, gabapentinoids, local anesthetics, acetaminophen, and other neuromodulatory pharmacologic agents. Continued research will be essential in the optimization of the MMA protocol for treating patients who undergo spine procedures.