Opioids have become the gold standard for treatment of severe pain in advanced disease, but adverse effects can affect the quality of life. Opioid-induced bowel dysfunction can lead to refractory constipation. Methylnaltrexone bromide is a peripherally acting mu antagonist and is indicated for the treatment of opioid-induced constipation in patients with advanced illness, when response to standard laxative therapy has been inefficacious. This pharmacology update will review the etiology, pathophysiology, and treatment of opioid-induced constipation, focused on methylnaltrexone as a novel treatment for refractory cases.