In this review paper, we discuss how the overarching concept of prehabilitation is applicable to alcohol dependence. Central to prehabilitation are the concepts of expected harm, risks, and proactive planning to eliminate the harm or cope with the risks. We review the evidence from animal models, psychological experimental studies, as well as pharmacological studies, on the potential risks and harms associated with medically assisted alcohol detoxification and the current treatment paradigm for alcohol dependence. Animal models provide an approximation mostly of the physical aspect of alcohol withdrawal and detoxification process and make predictions about the development of the phenomena in humans. Despite their limitations, these models provide good evidence that withdrawal from chronic ethanol use induces cognitive impairment, which is worsened by repeated bouts of withdrawal and that these impairments are dependent on the duration of alcohol withdrawal. Initial clinical observations with alcohol-dependent patients confirmed increased incidence of seizures. In recent years, accumulating evidence suggests that patients who have had repeated episodes of withdrawal also show changes in their affect, increased craving, as well as significant deterioration of cognitive abilities, when compared to patients with fewer withdrawals. Alcohol dependence is associated with tolerance and withdrawal, with neuroadaptations in γ-Aminobutyric Acid-A Receptor (GABA-A) and glutamatergic N-methyl-D-aspartate (NMDA) receptors playing key roles. It is suggested that dysregulation of the NMDA receptor system underpins alcohol-related memory impairments. Finally, we discuss the Structured Preparation for Alcohol Detoxification (SPADe) as an example of how prehabilitation has been applied in clinical practice. We discuss the importance of partial control over drinking as an interim step toward abstinence and early introduction of lifestyle changes for both the patient and the immediate environment prior to detoxification and while the patient is still drinking.