This article concentrates on recent evidence about opioid analgesics for persistent noncancer pain. Evidence confirms that opioids are drugs with a definite risk of adverse events. Therefore, before prescribing opioids, careful consideration must be given to be certain that the intended benefit of a particular opioid merits its use despite the potential side effects and to determine if the co-prescription of other pharmacologic agents could reduce the risk of adverse events. Strong opioids should be reserved for patients who fail to respond to other lower-risk options and only after proper consideration is given to the long-term consequences of strong opioid use. Problems associated with opioids dictate that more efficacious and safer drugs need to be found.