The mesolimbic dopamine system, of which the cell bodies are located in the ventral tegmental area, has been implicated in the physiology of reward and the related pathophysiology of drug abuse. This area has been a site of significant interest to study the effects of drugs of abuse and neurotransmitter systems implicated in the rewarding effects of these compounds. One important aspect of synaptic transmission is the ability of synapses to strengthen or weaken their connection as a consequence of synaptic activity. Recently, it has become apparent that this phenomenon is also present in the ventral tegmental area and that this may bear important functional consequences for the ways in which drugs of abuse assert their effect. Here, we will review the effects of neurotransmitter systems and drugs of abuse on cellular activity and synaptic transmission in the ventral tegmental area.