Brain plasticity refers to the ability of the brain to undergo structural and functional changes. It is a necessary process that allows us to adapt and learn from our environment and is fundamental to our survival. However, under certain conditions, these neuroadaptive responses can have adverse consequences. In particular, increasing evidence indicates that plastic processes are coopted by drugs of abuse, leading to addiction and associated drug-seeking behaviors. An extensive and diverse group of studies ranging from the molecular to the behavioral level has also strongly implicated glutamatergic neurotransmission as a critical mediator of experience-dependent synaptic plasticity. Thus, it is vital to understand how drugs of abuse interact and potentially alter glutamatergic neurotransmission and associated signal transduction processes. This review will focus on the cellular and molecular neuroscience of alcoholism, with emphasis on events at the glutamatergic postsynaptic density (PSD) and dendritic spine dynamics that appear to underlie much of the structural and functional plasticity of the CNS.