Drug addiction, also known as substance dependence, is a chronic, relapsing disorder characterized by 1) compulsion to seek and take the drug, 2) loss of control in limiting intake, and 3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented (defined here as dependence) (Koob and Le Moal 1997). Addiction and substance dependence, as currently defined in DSM-IV-TR (American Psychiatric Association 2000), will be used interchangeably throughout this chapter and refer to a final stage of a usage process that moves from drug use to addiction. Clinically, the occasional but limited use of a drug with the potential for abuse or dependence is distinct from escalated drug use and the emergence of a chronic drug-dependent state. An important goal of current neurobiological research is to understand the neuropharmacological and neuroadaptive mechanisms within specific neurocircuits that mediate the transition from occasional, controlled drug use to the loss of behavioral control over drug seeking and drug taking that defines chronic addiction.