Postoperative neurocognitive disorders (PNDs) encompass a spectrum of cognitive dysfunction in the perioperative period. PNDs can present with hypoactive symptoms such as lethargy, hyperactive symptoms such as confusion and disorientation or a mix of both. PNDs can affect patients of all ages; however, the incidence of PNDs increases significantly as patients age. It is important to promptly recognize PNDs as patients can have higher morbidity and mortality, longer hospital stays, higher readmissions rates, and additional testing/treatment after discharge. In this review, we explore the molecular basis involved in brain aging as well as the mechanisms involved in anesthesia exposure and the development of PNDs. Understanding the mechanisms behind brain aging and the parallels to the pathophysiology of PNDs such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic disruption are integral to mitigating the incidence and severity of PNDs. Current research suggests possible clinical targets for management such as dexmedetomidine and NSAIDs due to their abilities to combat harmful neuroinflammatory effects. Additionally, EEG-guided anesthesia, careful choice of anesthetics, and supportive measures can aid in mitigating PNDs. By understanding the mechanisms of brain aging, the risk factors for and pathophysiology of PNDs, we can better tailor our management of PNDs.