This review article discusses the efficacy and safety of various treatment options for perioperative multimodal analgesia. Postoperative pain is common and can lead to complications if not managed properly. While opioids are commonly used for pain management, they carry risks such as dependence and overdose. Multimodal analgesia, which combines multiple medications targeting different pain pathways, can effectively manage postoperative pain and reduce opioid use. The review covers common pharmacological treatments including gabapentinoids, opioids, alpha-2 agonists, ketamine, NSAIDs, and corticosteroids, as well as newer regional anesthetic techniques. Each medication has its own efficacy, risks, and benefits. Opioids are effective but have significant side effects, while NSAIDs can reduce opioid use but carry risks of gastrointestinal bleeding and cardiovascular events. Acetaminophen is generally safe but has limitations in patients with liver disease. Gabapentinoids are useful for neuropathic pain but have risks of CNS depression. Ketamine is effective for pain and reduces opioid use but can cause delirium and respiratory depression. Alpha-2 agonists like clonidine and dexmedetomidine reduce opioid use and postoperative delirium but can cause hypotension and bradycardia. Corticosteroids reduce inflammation and pain but can increase blood glucose and risk infection. Regional anesthesia techniques such as epidural, paravertebral, and TAP blocks are effective for pain management and reduce opioid use. The review emphasizes the importance of using multimodal strategies to minimize opioid use and improve patient outcomes.This review article discusses the efficacy and safety of various treatment options for perioperative multimodal analgesia. Postoperative pain is common and can lead to complications if not managed properly. While opioids are commonly used for pain management, they carry risks such as dependence and overdose. Multimodal analgesia, which combines multiple medications targeting different pain pathways, can effectively manage postoperative pain and reduce opioid use. The review covers common pharmacological treatments including gabapentinoids, opioids, alpha-2 agonists, ketamine, NSAIDs, and corticosteroids, as well as newer regional anesthetic techniques. Each medication has its own efficacy, risks, and benefits. Opioids are effective but have significant side effects, while NSAIDs can reduce opioid use but carry risks of gastrointestinal bleeding and cardiovascular events. Acetaminophen is generally safe but has limitations in patients with liver disease. Gabapentinoids are useful for neuropathic pain but have risks of CNS depression. Ketamine is effective for pain and reduces opioid use but can cause delirium and respiratory depression. Alpha-2 agonists like clonidine and dexmedetomidine reduce opioid use and postoperative delirium but can cause hypotension and bradycardia. Corticosteroids reduce inflammation and pain but can increase blood glucose and risk infection. Regional anesthesia techniques such as epidural, paravertebral, and TAP blocks are effective for pain management and reduce opioid use. The review emphasizes the importance of using multimodal strategies to minimize opioid use and improve patient outcomes.