Expanding elderly populations are a major social challenge in advanced countries worldwide and have led to a rapid increase in the number of elderly patients in intensive care units (ICUs). Innovative advances in medical technology have enabled lifesaving of patients in ICUs, but there remain various problems to improve their long-term prognoses. Post-intensive care syndrome (PICS) refers to physical, cognition, and mental impairments that occur during ICU stay, after ICU discharge or hospital discharge, as well as the long-term prognosis of ICU patients. Its concept also applies to pediatric patients (PICS-p) and the mental status of their family (PICS-F). Intensive care unit-acquired weakness, a syndrome characterized by acute symmetrical limb muscle weakness after ICU admission, belongs to physical impairments in three domains of PICS. Prevention of PICS requires performance of the ABCDEFGH bundle, which incorporates the prevention of delirium, early rehabilitation, family intervention, and follow-up from the time of ICU admission to the time of discharge. Diary, nutrition, nursing care, and environmental management for healing are also important in the prevention of PICS. This review outlines the pathophysiology, prevention, and future directions of PICS.