Pain is one of the most common reasons for patients to visit the emergency department and other acute care settings. Due to the extensive number of visits related to pain, ED clinicians across the globe and should be aware of the various therapeutic options available to them to treat patients with a variety of acute and chronic painful syndromes. With a huge improvement in understanding of the neurobiological aspect of pain by utilizing channels/enzymes/receptors concept, ED clinicians should consider patient-centered, pain syndrome-specific approach by using multimodal approach that include non-pharmacological modalities and pharmacological ones that include non-opioid and opioid analgesics. Additionally, availability and cost -effectiveness of analgesics need to be factored in treatment plan across the globe.