In the the past two decades the medical use of prescription opioids (POs), in particular oxycodone, increased up to 14-fold in the U.S. and Canada. The high consumption of these pain relievers also led to non-medical use and abuse of these substances which in turn resulted in a dramatic increase in the number of PO related fatalities and opioid dependent subjects. In the U.S. POs became the second most prevalent type of abused drug (4.5 million abusers; 1.7% of the population) after marijuana (8 million abusers) with currently 1.9 million (0.7% of the population) people dependent on opioid pain relievers. Pain relief was the leading motive for non-medical use in about 40% of the cases, but about half of non-medical PO users reported non-pain relief motives only, like to get high or to relax. Since 2011, there is a decline in the use and misuse of POs and reduction in painkiller overdose deaths in the U.S. probably due to the introduction of a variety of restrictive regulations. In Europe, the medical use of POs is increasing as well, but at a much slower rate than in the U.S. Moreover, in Europe non-medical use of POs and fatal PO incidents are (still) rare. The paper highlights and discusses the differences between Europe versus U.S. and Canada in an attempt to assess the risk of a PO abuse and overdose epidemic in Europe. It is concluded that the risk in Europe seems to be rather limited but vigilance is needed.