Abstract Regional anesthesia has become invaluable for the treatment of pain during and after a wide range of surgical procedures. However, its benefits in the nonsurgical setting have been less well studied. Regional anesthesia is an appealing modality for critically ill patients, providing focused and sustained pain control with beneficial systemic effect profiles. Indications for regional anesthesia in this patient group are not limited to surgical and postsurgical analgesia but expand to the management of trauma-related issues, medical conditions, and painful procedures at the bedside. Patients in the critical care unit present special challenges to the regional anesthesiologist, including coagulopathies, infections, immunocompromised states, sedation- and ventilation-associated problems, and factors potentially increasing the risk for systemic toxicity. This review is intended to evaluate the role of regional anesthesia in critically ill patients, to discuss potential benefits, and to provide a summary of the published evidence on the subject.