Postoperative delirium and cognitive decline are adverse events that occur frequently in elderly patients. Preexisting patient factors, medications, and various intraoperative and postoperative causes have been implicated in the development of postoperative delirium and cognitive decline. Despite previous studies identifying postoperative pain as a risk factor, relatively few clinical studies have compared the effect of common postoperative pain management techniques (IV and epidural) or opioid analgesics on postoperative cognitive status. A systematic search of the PubMed and CINAHL databases identified six studies comparing different opioid analgesics on postoperative delirium and cognitive decline and five studies comparing IV and epidural routes of administering analgesia. Meperidine was consistently associated with an increased risk of delirium in elderly surgical patients, but the current evidence has not shown a significant difference in postoperative delirium or cognitive decline among other more frequently used postoperative opioids such as morphine, fentanyl, or hydromorphone. The available studies also suggest that IV or epidural techniques do not influence cognitive function differently. However, future investigations of sufficient study size and more standardized methods of defining outcomes are necessary to confirm the current findings.