Neuromuscular blocking agents (NMBAs) can be an effective modality to address challenges that arise daily in the intensive care unit (ICU). These medications are often used to optimize mechanical ventilation, facilitate endotracheal intubation, stop overt shivering during therapeutic hypothermia following cardiac arrest, and may have a role in the management of life-threatening conditions such as elevated intracranial pressure and status asthmaticus (when deep sedation fails or is not tolerated). However, current NMBA use has decreased during the last decade due to concerns of potential adverse effects such as venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, and even residual paralysis following cessation of NMBA use. It is therefore essential for clinicians to be familiar with evidence-based practices regarding appropriate NMBA use in order to select appropriate indications for their use and avoid complications. We believe that selecting the right NMBA, administering concomitant sedation and analgesic therapy, and using appropriate monitoring techniques mitigate these risks for critically ill patients. Therefore, we review the indications of NMBA use in the critical care setting and discuss the most appropriate use of NMBAs in the intensive care setting based on their structure, mechanism of action, side effects, and recognized clinical indications. Lastly, we highlight the available pharmacologic antagonists, strategies for sedation, newer neuromuscular monitoring techniques, and potential complications related to the use of NMBAs in the ICU setting.