Potent opioids are excellent painkillers but their use is hampered by side-effects such as nausea, vomiting, bowel dysfunction, urinary retention, pruritus, sedation and respiratory depression. Co-analgesics are often combined with opioids to reduce the prevalence of these unwanted effects while maintaining or even improve the quality of analgesia. A search of the recent literature demonstrated that peripheral opioid antagonists are able to reduce opioid-induced bowel dysfunction without interfering with analgesia. Dexmedetomidine, gabapentin, and ketamine significantly reduce opioid consumption but have no effect on the incidence of opioid side-effects. In contrast, intravenous lidocaine and corticosteroids not only produce an opioid-sparing but also a significant reduction in the occurrence of postoperative ileus and nausea and vomiting. It remains unclear whether the perioperative use gabapentin, ketamine and corticosteroids has an effect on the development of postsurgical chronic pain states.