Survivors of critical illness often experience new or worsening impairments of physical, cognitive, and/or mental health, referred to as Post-Intensive Care Syndrome (PICS). Such impairments can be long-lasting and negatively affect survivors’ quality of life. Early rehabilitation in the intensive care unit (ICU), while patients remain on life-support therapy, may reduce the complications associated with PICS. This article addresses evidence-based rehabilitation interventions to reduce the physical and mental health impairments associated with PICS. Implementation of effective early rehabilitation interventions targeting physical impairment requires consideration of five factors: barriers, benefits, feasibility, safety, and resources. Mental health impairments may be addressed by use of the following interventions: use of ICU diaries, early in-ICU psychological interventions, and post-ICU coping skills training. In both cases, a multidisciplinary team-based approach is paramount to successful incorporation of early rehabilitation into routine practice in the ICU.