Critically ill patients commonly experience pain, and the provision of analgesia is an essential component of intensive care unit (ICU) care. Opioids are the mainstay of pain management in the ICU but are limited by their adverse effects, risk of addiction and abuse, and recent drug shortages of injectable formulations. A multimodal analgesia approach, utilizing nonopioid analgesics as adjuncts to opioid therapy, is recommended since they may modulate the pain response and reduce opioid requirements by acting on multiple pain mediators. Nonopioid analgesics discussed in detail in this article are acetaminophen, α-2 receptor agonists, gabapentinoids, ketamine, lidocaine, and nonsteroidal anti-inflammatory drugs. This literature review describes the clinical pharmacology, supportive ICU and relevant non-ICU data, and practical considerations associated with the administration of nonopioid analgesics in critically ill adult patients.