Critical illness can be lethal and devastating to survivors. Improvements in acute care have increased the number of intensive care unit (ICU) survivors. These survivors confront a range of new or worsened health states that collectively are commonly denominated post–intensive care syndrome (PICS). These problems include physical, cognitive, psychological, and existential aspects, among others. Burgeoning interest in improving long-term outcomes for ICU survivors has driven an array of potential interventions to improve outcomes associated with PICS. To date, the most promising interventions appear to relate to very early physical rehabilitation. Late interventions within aftercare and recovery clinics have yielded mixed results, although experience in heart failure programs suggests the possibility that very early case management interventions may help improve intermediate-term outcomes, including mortality and hospital readmission. Predictive models have tended to underperform, complicating study design and clinical referral. The complexity of the health states associated with PICS suggests that careful and rigorous evaluation of multidisciplinary, multimodality interventions—tied to the specific conditions of interest—will be required to address these important problems.