The number of patients who are receiving long-term opioids has increased significantly over the last two decades. Perioperative management of such patients is often challenging and requires meticulous planning and multidisciplinary approach for successful outcome. It is important to take into account the psychological and physical dependence as well as associated comorbidities while anesthetizing these patients. It is equally essential to ensure that the baseline requirements of opioids are met independent of the anesthetic technique used. Use of regional blocks and non-opioid medications is found to reduce the opioid requirements and enhance recovery process. A small number of patients who are chronic opioid dependents and abusers may require very high doses of opioid medications in the immediate postoperative period for effective pain relief. Abrupt withdrawal of opioids in the perioperative period can result in withdrawal syndrome and hence must be avoided. This chapter delves into opioid epidemic, opioid dependence, associated comorbidities, anesthetic challenges, and perioperative management of opioid dependent patients.