Abstract Effective pain management is vital for critically ill patients, particularly post-surgery or trauma, as it can mitigate the stress response and positively influence morbidity and mortality rates. The suboptimal treatment of pain in Intensive Care Unit (ICU) patients is often due to a lack of education, apprehensions about side effects, and improper use of medications. Hence, the engagement of pain management and anesthesiology experts is often necessary. While opioids have been traditionally used in pain management, their side effects make them less appealing. Local anesthetics, typically used for anesthesia and analgesia in surgical procedures, have carved out a unique and crucial role in managing pain and other conditions in critically ill patients. This work aims to offer a comprehensive overview of the role, advantages, challenges, and evolving practices related to the use of local anesthetics in ICUs. The ability to administer local anesthetics continuously makes them a suitable choice for controlling pain in the upper and lower extremities, with fewer side effects. Epidural analgesia is likely the most used regional analgesic technique in the ICU setting. It is primarily indicated for major abdominal and thoracic surgeries, trauma, and oncology patients. However, it has contraindications and complications, so its use must be carefully weighed. Numerous challenges exist regarding critically ill patients, including renal and hepatic failure, sepsis, uremia, and the use of anticoagulation therapy, which affect the use of regional anesthesia for pain management. Appropriate timing and indication are crucial to maximizing the benefits of these methods. The advent of new technologies, such as ultrasonography, has improved the safety and effectiveness of neuraxial and peripheral nerve blocks, making them feasible options even for heavily sedated patients in ICUs.