This review article discusses the efficacy and safety of various pharmacological and regional anesthesia techniques for perioperative multimodal analgesia. It highlights the importance of managing postoperative pain to prevent complications and improve patient outcomes. The article covers common pharmacological treatments such as opioids, gabapentinoids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, alpha-2 agonists, corticosteroids, and lidocaine. Each treatment option is evaluated for its efficacy, risks, and benefits. Additionally, the article reviews newer regional anesthetic techniques, including epidural anesthesia, paravertebral block, upper limb nerve blocks, transverse abdominis plane block, quadratus lumborum block, and erector spinae block. The use of high echogenicity needles, local anesthetic adjuncts, continuous infusion, long-acting local anesthetics, and considerations for local anesthetic volume are also discussed. The article emphasizes the importance of a multimodal approach to pain management, which can reduce opioid usage and improve patient outcomes.This review article discusses the efficacy and safety of various pharmacological and regional anesthesia techniques for perioperative multimodal analgesia. It highlights the importance of managing postoperative pain to prevent complications and improve patient outcomes. The article covers common pharmacological treatments such as opioids, gabapentinoids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, alpha-2 agonists, corticosteroids, and lidocaine. Each treatment option is evaluated for its efficacy, risks, and benefits. Additionally, the article reviews newer regional anesthetic techniques, including epidural anesthesia, paravertebral block, upper limb nerve blocks, transverse abdominis plane block, quadratus lumborum block, and erector spinae block. The use of high echogenicity needles, local anesthetic adjuncts, continuous infusion, long-acting local anesthetics, and considerations for local anesthetic volume are also discussed. The article emphasizes the importance of a multimodal approach to pain management, which can reduce opioid usage and improve patient outcomes.