While intraoperative mortality has diminished greatly over the last several decades, the risk of death within 30 days of surgery remains stubbornly high and is ultimately related to perioperative organ failure. Perioperative strokes, while rare (<2% in noncardiac surgery), are associated with a more than 10-fold increase in mortality. Rapid identification and treatment are key to maximizing long-term outcomes. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are separate but related perioperative neurological disorders, both of which are associated with poor long-term outcomes. To date, there are few known interventions that can ameliorate the risk of perioperative central nervous system dysfunction. Major adverse cardiac events (MACE) are a major contributor to adverse clinical outcomes following surgical procedures. Recently, advances in diagnostic strategies (eg, high-sensitivity cardiac troponin [hs-cTn] assays) have improved our understanding of MACE. Recently, the dabigatran in patients with myocardial injury after noncardiac surgery (MINS; Management of myocardial injury After NoncArdiac surGEry) trial demonstrated that a direct thrombin inhibitor could improve outcomes following MINS. While the risk of acute respiratory distress syndrome (ARDS) after surgery is approximately 0.2%, other less severe complications (eg, pneumonia, reintubation) are closer to 2%. While intensive care unit (ICU) concepts related to ARDS have migrated into the operating room, whether or not adverse pulmonary outcomes impact long-term outcomes in surgical patients remains a matter of debate. The standardization of acute kidney injury (AKI) definition has improved the ability of clinicians to measure and study the incidence of this important source of perioperative morbidity. AKI is associated with increased mortality as well as nonrenal morbidity (eg, myocardial infarction) after major surgery. Gastrointestinal complications after surgery range from ileus (common in abdominal procedures and associated with an increased length of stay) to less common complications such as mesenteric ischemia and gastrointestinal bleeding, both of which are associated with very high mortality. Outside of cardiothoracic surgery, the incidence of perioperative hepatic injury is not well described but, in this population, is associated with worsened long-term outcomes. Hyperglycemia is a common perioperative complication and occurs in patients undergoing both cardiac and noncardiac surgery. Both hyper- and hypoglycemia are associated with worsened long-term outcomes in cardiac and noncardiac surgery. Better diagnosis and increased understanding of perioperative organ injury has led to an increased appreciation for the specific role that particular organ systems play in poor long-term outcomes and has set the stage for targeted therapeutic interventions.