Purpose of Review The opioid epidemic in the USA has led to a rise in opioid-related gastrointestinal (GI) side effects that are often difficult to diagnose and treat. The aim of this report is to discuss opioid pathophysiology, opioid-related GI side effects, clinical presentation, and diagnostic criteria and to review the current pharmacotherapy available. Recent Findings Opioid-related GI disorders are increasingly recognized and include, but are not limited to, opioid-induced esophageal dysfunction (OIED), gastroparesis, opioid-induced constipation (OIC), narcotic bowel syndrome (NBS), acute post-operative ileus, and anal sphincter dysfunction. Treatment of these conditions is challenging. OIC has the most available pharmacotherapy for treatment, including classical laxatives, peripherally acting μ-receptor antagonists (PAMORAs), novel therapies (lubiprostone, prucalopride- 5-HT agonist), and preventative therapies (PR oxycodone/naloxone). Summary The gastrointestinal effects of opioid therapy are variable and often debilitating. While medical management for some opioid-related GI side effects exists, limiting or completely avoiding opioid use for chronic non-cancer pain will mitigate these effects most effectively.