Over the past two decades, as the prevalence of chronic pain and health care costs have exploded, an opioid epidemic with adverse consequences has escalated. Efforts to increase opioid use and a campaign touting the alleged undertreatment of pain continue to be significant factors in the escalation. Many arguments in favor of opioids are based solely on traditions, expert opinion, practical experience and uncontrolled anecdotal observations. Over the past 20 years, the liberalization of laws governing the prescribing of opioids for the treatment of chronic non-cancer pain by the state medical boards has led to dramatic increases in opioid use. This has evolved into the present stage, with the introduction of new pain management standards by the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) in 2000, an increased awareness of the right to pain relief, the support of various organizations supporting the use of opioids in large doses, and finally, aggressive marketing by the pharmaceutical industry. These positions are based on unsound science and blatant misinformation, and accompanied by the dangerous assumptions that opioids are highly effective and safe, and devoid of adverse events when prescribed by physicians. Results of the 2010 National Survey on Drug Use and Health (NSDUH) showed that an estimated 22.6 million, or 8.9% of Americans, aged 12 or older, were current or past month illicit drug users, The survey showed that just behind the 7 million people who had used marijuana, 5.1 million had used pain relievers. It has also been shown that only one in 6 or 17.3% of users of non-therapeutic opioids indicated that they received the drugs through a prescription from one doctor. The escalating use of therapeutic opioids shows hydrocodone topping all prescriptions with 136.7 million prescriptions in 2011, with all narcotic analgesics exceeding 238 million prescriptions. It has also been illustrated that opioid analgesics are now responsible for more deaths than the number of deaths from both suicide and motor vehicle crashes, or deaths from cocaine and heroin combined. A significant relationship exists between sales of opioid pain relievers and deaths. The majority of deaths (60%) occur in patients when they are given prescriptions based on prescribing guidelines by medical boards, with 20% of deaths in low dose opioid therapy of 100 mg of morphine equivalent dose or less per day and 40% in those receiving morphine of over 100 mg per day. In comparison, 40% of deaths occur in individuals abusing the drugs obtained through multiple prescriptions, doctor shopping, and drug diversion. The purpose of this comprehensive review is to describe various aspects of crisis of opioid use in the United States. The obstacles that must be surmounted are primarily inappropriate prescribing patterns, which are largely based on a lack of knowledge, perceived safety, and inaccurate belief of undertreatment of pain.