Alcohol withdrawal is a syndrome that is the result of adaptive changes in the brain secondary to chronic alcohol use and is associated with changes in many neurotransmitter, neuropeptide, and hormonal systems. Long-term exposure to ethanol leads to an imbalance in different excitatory (especially glutamate, a major excitatory amino acid), and inhibitory neurotransmitter (especially GABA, a major inhibitory amino acid) systems. When alcohol consumption is reduced or completely ceases, these imbalances are behaviorally expressed in the form of alcohol withdrawal. Symptoms of alcohol withdrawal are mainly associated with the hypofunction of GABA receptors and enhanced function of NMDA receptors. The imbalance between receptors may be exacerbated by repeated withdrawal. Some of these alterations may last for months following alcohol cessation and cause symptoms of protracted alcohol withdrawal, which may contribute to the continuation of the cycle of alcohol addiction relapses. The search for biological alterations during alcohol withdrawal may not only render some important insights into the pathophysiology of alcohol dependence, but might also identify new targets for the treatment of alcohol withdrawal symptoms and for preventing relapses following withdrawal. Therapists specializing in the treatment of addiction should be cognizant of the underlying biological mechanisms of alcohol withdrawal in order to more adequately understand the physiopathology of substance dependence in general. In this paper, we will review the changes in the inhibitory and excitatory neurotransmitter systems involved in alcohol withdrawal, and we will discuss their roles in the development of alcohol dependence.