The neurobiological processes that underlie initial use of drugs of abuse and the transition to drug abuse, addiction, and dependence are poorly understood. Intrinsic and drug-related alterations in complex brain functions such as motivation, learning, memory, reward, attention, and arousal seemingly underlie the process of drug abuse and addiction. This discussion focuses on the use of functional brain imaging techniques such as positron emission tomography and functional magnetic resonance imaging to define the roles of the amygdala in the sequence of behavioral processes that span initial drug use to addiction and its consequences. The functional images of the human amygdala demonstrate or implicate this limbic structure in the processes of reward learning and memory, conditioned reward and emotion dysregulation related to drug use, and the transition to addiction. While these roles of the amygdala reflect its involvement in the actions of large-scale neural systems comprising cortical and subcortical structures, its important roles as a neural substrate mediating or modulating behaviors related to initial drug use to addiction, and its personal and social consequences, are increasingly defined by functional brain imaging studies.