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Background: Wernicke-Korsakoff syndrome (WKS) is a severe neurological disorder caused by thiamine deficiency leading to significant impairments in cognition, strength, and coordination. Minimal literature is available regarding the physical rehabilitation of patients with WKS. Thus, this case report provides a critical analysis, in light of available evidence and theory, of the comprehensive physical therapy interventions utilized in the management of a complex patient presenting with alcohol-induced Wernicke-Korsakoff syndrome within an inpatient rehabilitation setting. Case Description: The patient was a 40-year-old female admitted to inpatient rehabilitation following acute hospitalization for sepsis. She was diagnosed with Wernicke-Korsakoff syndrome due to her history of alcoholism and presentation of cognitive impairments, cerebellar deficits, and weakness. Clinical Impression: The patient demonstrated decreased motor coordination, balance, strength, proprioception, and activity tolerance. She was evaluated and treated by occupational, speech, and recreational therapy to fully address her biopsychosocial needs. Intervention: Physical therapy interventions addressed strength, balance, coordination, and functional mobility with consideration to the complex neuropsychological components present in a patient with WKS. Adjunctive strategies addressing movement-related anxiety included the use of music and cognitive tasks tailored to the patient’s interests. Outcome Measures: Patient progress was measured via the Inpatient Rehabilitation Facility Patient Assessment Instrument (IRF-PAI) which specifically measures cognition, activities of daily living (ADLs), and functional mobility. Discussion: This case report examines available pertinent literature and provides an illustration of a positive rehabilitation outcome for an individual with WKS. Additionally, this report discusses the incorporation of errorless learning techniques, music therapy, and structured environmental considerations as practical solutions to address the neuropsychological barriers often impeding the physical rehabilitation of individuals with WKS.