The role of the liver in drug metabolism makes individuals with hepatic dysfunction more susceptible to adverse drug reactions, necessitating careful consideration in analgesic selection and dosing. Acetaminophen, despite being a common cause of liver failure, is considered safe within recommended dosages. Nonsteroidal anti-inflammatory drugs (NSAIDs), while effective, pose risks in cirrhosis due to complications like renal failure and gastrointestinal bleeding. Cyclooxygenase-2 inhibitors have limited data, and their use is discouraged due to cardiovascular concerns. Opiates, though potent, require cautious use in cirrhosis due to altered metabolism, potential adverse effects, and the risk of addiction. Tricyclic antidepressants like nortriptyline and desipramine can be utilized for neuropathic pain, while SSRIs and SNRIs are not recommended. Anticonvulsants such as gabapentin and pregabalin are preferred for neuropathic pain, with gabapentin being the first-line choice. Topical analgesics, including NSAIDs, lidocaine, and rubefacients, are deemed safe for use in cirrhosis, offering localized relief with minimal systemic effects. Nonpharmacological approaches addressing medical, psychological, and socio-economic factors are crucial adjuvants to analgesic therapy in advanced liver diseases. Physiotherapy, psychotherapy, behavioral therapy, relaxation techniques, acupuncture, and traditional practices like yoga and massage, as well as novel modalities, contribute to a holistic pain management strategy. This review provides healthcare professionals with valuable insights into the complex landscape of analgesic therapy in cirrhosis. Meticulous consideration of drug metabolism, hepatic safety, and individual patient factors is paramount in optimizing pain management strategies for this challenging patient population.