Critically ill patients are at risk for several secondary complications, including delirium and long-term cognitive impairment. The exact mechanisms of delirium and ICU-related cognitive decline are not fully understood; however, the authors review several recent investigations that have proposed plausible explanations. This article also includes several practical guidelines for the identification and management of delirium to aid in the development and implementation of clinical procedures that will lower the risk for ICU delirium and cognitive decline.