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Acute kidney injury (AKI) and intensive care unit–acquired weakness (ICU-AW) are 2 frequent complications of critical illness that, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness—a major source of ICU morbidity—has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care toward improving long-term functional outcomes of ICU survivors. We begin our review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI treated with kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. We then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein …