Pain management in patients with cirrhosis is a difficult clinical challenge for health care professionals, and few prospective studies have offered an evidence-based approach. In patients with end-stage liver disease, adverse events from analgesics are frequent, potentially fatal, and often avoidable. Severe complications from analgesia in these patients include hepatic encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding, which can result in substantial morbidity and even death. In general, acetaminophen at reduced dosing is a safe option. In patients with cirrhosis, nonsteroidal anti-inflammatory drugs should be avoided to avert renal failure, and opiates should be avoided or used sparingly, with low and infrequent dosing, to prevent encephalopathy. For this review, we searched the available literature using PubMed and MEDLINE with no limits.