Postoperative pain is prevalent and often undertreated. There is a risk that untreated or suboptimally treated postoperative pain may transition into chronic postoperative pain, which can be challenging to treat. Clinical guidelines recommend the use of multimodal analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and, in some cases, opioids. NSAIDs are a broad class of drugs with different attributes such as cyclo-oxygenase (COX)-1 or COX-2 selectivity, onset of action, and analgesic potency. NSAIDs are associated with gastrointestinal and cardiovascular side effects and should be administered at the lowest effective dose for the shortest effective duration but can be effective in postoperative pain. The role of opioids in postoperative analgesia is long-standing but has recently come under scrutiny. Opioids are often used in multimodal analgesic combinations in such a way as to minimize the total consumption of opioids without sacrificing analgesic benefit. Special clinical considerations are required for surgical patients already on opioid regimens or with opioid use disorder. A particularly useful fixed-dose combination product for postoperative analgesia is dexketoprofen-tramadol, which confers safe and effective postoperative pain control and reduces the risk of persistent postoperative pain.