Pain is a common complaint precipitating emergency department (ED) visit, occurring in more than half of patient encounters. While opioids are effective for acute pain management in the Emergency Department (ED), the associated adverse effects, including respiratory and central nervous system depression, nausea, vomiting, and constipation, and physical manifestations of use, including tolerance, dependence and misuse leading to overdose and death, accentuate the need for non-opioid alternatives and/or multi-modal pain control. This review will provide examples of non-opioid pain management strategies and multimodal regimens for treatment of acute pain in the ED.