The NSAIDs and opioids figure prominently in the daily practice of EM. The gastrointestinal risks of NSAIDs are reduced by co-administration of gastroprotective therapy such as misoprostol or, preferably, proton pump inhibitors. The combination of NSAIDs and opioids fails to accrue additive (or synergistic) analgesic results. NSAIDs (and acetaminophen) will always claim one advantage over opioids: antipyresis. For most patients, the potential problems with opioids have little to do with efficacy in relieving pain. For short-term use as prescribed from the ED, the analgesic benefits of the opioids will counterbalance the risks foremost pregnant patients with pain uncontrollable by other means. Since most opioids are excreted to some degree in breast milk, opioids are best avoided in breastfeeding mothers. The controversy surrounding meperidine (pethidine) use in the ED is hard for acute care providers to avoid.